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Theoretical analysis of anticancer cellular effects of glycoside amides
Vasil Tsanov, Hristo Tsanov
ABSTRACT
Background: This article is a continuation of Theoretical Analysis for the Safe Form and Dosage of Amygdalin Product
and Theoretical Study of the Process of Passage of Glycoside Amides through the Cell Membrane of Cancer Cell. They
consider some possible natural modifications and hypothesize that it is not nitrile glycosides that have antitumor
properties, but their amide / carboxyl derivatives. The possibility of using this circumstance in conservative oncology is
also considered. A mechanism for crossing the cell membrane and overcoming the immune functions of the cancer cell
is presented.
The physiologically active cancer cell itself is quite inert to external influences. It is far more stable than any
physiologically active structural and/or functional organismal cell. Its defenses are discussed in detail in the article, and
its main weakness was defined, namely: the cancer cell feeds mainly on carbohydrates and/ or carbohydrate complexes.
In an effort to preserve its gene set, it has evolved to counteract biologically active substances by maximally preventing
its passage through its cell membrane.
It is this property that could be used to minimize its effect on the whole body. In the same article, based on theoretical
calculations and literature references, a hypothesis is stated: cancers could turn from severe infectious to controlled
chronic ones (similar to diabetes, chronic hepatitis, etc.).
Objective: The pharmaceutical form allows deviation from the chemically pure substance. It is a convenient and at the
same time accessible (from a financial and/or technological point of view) form for admission by patients.
Due to the great variety of natural glycosamide nitriles (starting material for the production of amide/ carboxylic acid),
modern pharmacology allows their combined intake by chemical nature and concentration of the active form crossing
the cell membrane.
Natural nitrile glycosides hydrolyzed to amide/carboxylic acid are still unexplored, but with great theoretical potential.
As biologically active substances, these compounds also have significant toxicity. One of the purposes of this article
is to organize laboratory tests on animals.
Methods: A comparative analysis is performed on the basis of stoichiometric calculations for the concentration of the
active form and the prediction of the bioactivity. For this purpose, the following methodology is applied: Data analysis
for active anticancer cell molecular form and Determination of the drug dose. The derived chemicals obtained
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immediately after the passage of glycosamide across the cancer cell membrane are: (R)-2-hydroxy-2-phenylacetamide,
(R)-2-hydroxy-2-(4-hydroxyphenyl)acetamide, (R)-2-hydroxy-2-(3-hydroxyphenyl)acetamide, 2-hydroxy-2-
methylpropanamide, (S)-2-hydroxy-2-methylbutanamide, 2-hydroxy-3-methylbut-2-enamide, (2Z,4E)-4-(2-amino-
1-hydroxy-2-oxoethylidene)hex-2-enedioic acid, (S)-1-hydroxycyclopent-2-ene-1-carboxamide, (1S,4S)-1,4-
dihydroxycyclopent-2-ene-1-carboxamide, (1R,4R)-1,4,5-trihydroxycyclopent-2-ene-1-carboxamide, (Z)-2-
((4S,6R)-4,6-dihydroxycyclohex-2-en-1-ylidene)acetamide, (R)-2-hydroxy-3-methylbutanamide, (E)-2-((4S,5R,6R)-
4,5,6-trihydroxycyclohex-2-en-1-ylidene)acetamide, (Z)-2-((4R,5R,6S)-5,6-dihydroxy-4-methoxycyclohex-2-en-1-
ylidene)acetamide, (E)-2-((4R,6S)-4,6-dihydroxycyclohex-2-en-1-ylidene)acetamide и (E)-2-((4S,5R,6R)-4,5,6-
trihydroxycyclohex-2-en-1-ylidene)acetamide.
Results: The use of two or more pharmaceutical forms would not prevent their penetration subject to the mass ratios
between the active antitumor amide and the active carboxyl transfer form.
Conclusion: Amides resulting from the hydrolysis of nitrile glycosides would have the ability to cross the cell membrane
of a cancer cell and thus cause its cellular response. The pharmaceutical form must represent the exact amide / carboxylic
acid ratio for the corresponding active anticancer cell form.
Keywords: anticancer cellular effects, glycoside amides, Druglikeness
1. BACKGROUND
This article is a continuation of Theoretical Analysis for the Safe Form and Dosage of Amygdalin
Product [1] and Theoretical Study of the Process of Passage of Glycoside Amides through the Cell Membrane
of Cancer Cell [2]. They consider some possible natural modifications and hypothesize that it is not nitrile
glycosides that have antitumor properties, but their amide / carboxyl derivatives. The possibility of using this
circumstance in conservative oncology is also considered. Some dosage forms (P.O.) and their concentrations
are proposed. A mechanism for crossing the cell membrane and overcoming the immune functions of the
cancer cell is presented.
The physiologically active cancer cell itself is quite inert to external influences. It is far more stable than
any physiologically active structural and/or functional organismal cell. Its defenses are discussed in detail in
the article [2], and its main weakness was defined, namely: the cancer cell feeds mainly on carbohydrates and/
or carbohydrate complexes. In an effort to preserve its gene set, it has evolved to counteract biologically active
substances by maximally preventing its passage through its cell membrane.
It is this property that could be used to minimize its effect on the whole body. In the same article, based
on theoretical calculations and literature references, a hypothesis is stated: cancers could turn from severe
infectious to controlled chronic ones (similar to diabetes, chronic hepatitis, etc.)
Regardless of whether the cancer cell is active and/or already has suppressed physiological functions, it
also has its corresponding cellular effect: proliferation [3] (including in combination with Wartburg’s effects
[4]), invasion [5], migration [6], metastasis [7], adhesion [8], cell cycle [9], cytotoxicity [10] and apoptosis [11] or
a combination of two or more simultaneous actions.
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Tabl. 1. Specific antitumor mechanisms of amygdalin in different tumors
Types
Cell lines
Dosage of
amygdalin
[mg/mL]
Treatment time
Cellular Effects
Lung cancer
H1299
PA
2.5 ÷ 5
48 hours
proliferation, invasion,
migration
Bladder cancer
UMUC‐3
RT112
TCCSUP
10
24 hours or 2 weeks
proliferation, adhesion,
invasion,
migration, cell cycle,
cytotoxicity
Renal cell
carcinoma
Caki‐1
KTC‐26
A498
10
24 hours or 2 weeks
proliferation, apoptosis,
adhesion,
cell cycle
Prostate cancer
LNCaP
DU‐145
PC3
0.1 ÷ 20
24 hours
proliferation, apoptosis,
cell
cycle
Cervical cancer
Hela cell
10 ÷ 20
24 hours
proliferation, apoptosis
Colon cancer
SNU‐C4
5
24 hours
proliferation, cell cycle,
cytotoxicity
cell cycle-related gene:
Promyelocytic
leukemia
HL‐60
1 ÷ 20
48 hours
proliferation, apoptosis
combinate with β-glucosidase
Breast Cancer
Hs578T
MDA‐MB‐231
ER‐positive MCF7
10 ÷ 40
24 hours
cytotoxicity, apoptosis,
adhesion
The information is provided by Shi [12] et al. They are summarized by studies of: Qian et al. [13], Makarevic et al. [14÷16], Syrigos et al.
[17], Juengel et. al. [18], Chang et al. [19], Chen et al. [20], Park et al. [21], Lee et al. [22] and Hee-Young et al. [23]
Data in Tablе 1 are applicable to the use of "pure" unmodified Amygdalin [§1.2 of article 1] and
concentrations consistent with its nitrile chemical nature.
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When using an amide/carboxyl dosage form [§4 of article 1 and §5 of article 2] “|working”
concentrations are increased up to four times for amygdalin (for individual amide/carboxyl derivatives of
nitrile glycosides up to 7 times) and the treatment time could be extended to months. Only this way it could
fulfill the condition for the active molecule to pass through the cell membrane of the cancer cell. (Figure 1).
DOI: 10.6084/m9.figshare.23903805.v1
Fig. 1. Scheme of the chemical relationship between basic and hydrolyzed forms of amide and carboxyl
forms of nitrile glycosides under different conditions in vivo around and in cancer cell
Therefore, the possible chemical apoptosis (or other type of cellular reaction) will occur independently
of all enzymes synthesized according to instructions from cancer DNA (for example, as - linamarase gene to
linamarase).
2. OBJECTIVE
The pharmaceutical form allows deviation from the chemically pure substance. It is a convenient and
at the same time accessible (from a financial and/or technological point of view) form for admission by
patients. It is not necessary to use an "ideal" pure active substance (including a specific isomeric form).
Due to the great variety of natural glycosamide nitriles (starting material for the production of amide/
carboxylic acid), modern pharmacology allows their combined intake by chemical nature and concentration
of the active form crossing the cell membrane.
The different action of these molecules on a physiologically active cancer cell (proliferation, invasion,
migration, adhesion, invasion, cell cycle, cytotoxicity, etc.) allows their joint influence.
Determining the optimal concentration is essential for the reliability of the dosage form. That is why
most of the already known and well-established methodologies for predicting biological activity, toxicity and
drug action must be considered in great detail.
For the purposes of the present study, the article also examines the subsequent processes of penetration
of glycosamides into the cancer cell and its cellular effects - especially the general toxicity of the cancer cell.
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3. METHODS
Amide/carboxylic acid hydrolyzed natural nitrile glycosides can be conditionally divided into 16 groups
according to the active anticancer cell molecules forms (AACF) secreted inside the cancer cell. Some of the
groups have more than one homologous representative and it is necessary to find the optimal one for
application (in terms of toxicity, working concentration, time of administration, etc.). Methods for non-
laboratory and non-clinical assessment are applied, which are as close as possible to the real conditions and
minimize as much as possible the errors in the theoretical research.
A comparative analysis is performed on the basis of stoichiometric calculations for the concentration of
the active form and the prediction of the bioactivity. For this purpose, the following methodology is applied:
3.1. Data analysis for active anticancer cell molecular form
The derived chemicals obtained immediately after the passage of glycosamide across the cancer cell
membrane [§6 of article 1] are: (R)-2-hydroxy-2-phenylacetamide, (R)-2-hydroxy-2-(4-
hydroxyphenyl)acetamide, (R)-2-hydroxy-2-(3-hydroxyphenyl)acetamide, 2-hydroxy-2-methylpropanamide,
(S)-2-hydroxy-2-methylbutanamide, 2-hydroxy-3-methylbut-2-enamide, (2Z,4E)-4-(2-amino-1-hydroxy-2-
oxoethylidene)hex-2-enedioic acid, (S)-1-hydroxycyclopent-2-ene-1-carboxamide, (1S,4S)-1,4-
dihydroxycyclopent-2-ene-1-carboxamide, (1R,4R)-1,4,5-trihydroxycyclopent-2-ene-1-carboxamide, (Z)-
2-((4S,6R)-4,6-dihydroxycyclohex-2-en-1-ylidene)acetamide, (R)-2-hydroxy-3-methylbutanamide, (E)-2-
((4S,5R,6R)-4,5,6-trihydroxycyclohex-2-en-1-ylidene)acetamide, (Z)-2-((4R,5R,6S)-5,6-dihydroxy-4-
methoxycyclohex-2-en-1-ylidene)acetamide, (E)-2-((4R,6S)-4,6-dihydroxycyclohex-2-en-1-
ylidene)acetamide и (E)-2-((4S,5R,6R)-4,5,6-trihydroxycyclohex-2-en-1-ylidene)acetamide. The analysis
is conducted in several phases:
3.1.1. Determining the exact molecular shape
Here is considered the geometry of the molecule [24] on the basis of literature data [25] and MM2 [26],
and as a corrective is taken into account and MMFF94 [27].
3.1.1.1. Druglikeness of the pharmaceutical form
Amides/carboxylic acids obtained by hydrolysis of natural nitrile glycosides are analyzed. Their
concentrations and quantitative ratios are not considered here, but only the nature of the substances. Chemical
ratios affecting biological activity were compared by Molinspiration Drug Property [28]: GPCR ligand [29],
Ion channel modulator [30], Kinase inhibitor [31], Nuclear receptor ligand [32], Protease inhibitor [33, 34] and
Enzyme inhibitor [35÷37] in order to characterize the overall Druglikeness [38]. The data are presented in
tabular form and the values that cover the minimum requirements for the respective indicator are marked in
light green, and in more saturated green - those covering the optimal requirements. In order to consider that a
substance has the bio-activity of a medicinal product, it needs to have at least two of the sets of minimum
values.
The results are extremely insufficient and too dualistic. They are relatively comparative and not give
information about possible deviations in the direction of toxicity. Other (mutually exclusive) methodologies
for drug evaluation are also considered.
3.1.1.2. Pharmacological and biological activity of oral active drugs
The proposed pharmaceutical molecular form is recommended to be administered in the body in a solid
state by mouth [§5 of Article 1]. The main goal here is not to precisely define the drug "strength", but to
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compare, empirically, indicators for the evaluation of molecules and the interchangeability of the starting
precursors. Therefore, it is not the absolute accuracy that matters, but only the extremely strict repeatability
of the assessment methodologies. No deviation in rounding of values affecting the precise statistical
processing of the results is allowed. Calculations [39÷47] are performed with the drug-likeness tool (DruLiTo
2018 [48]) (NIPER S.A.S., Nagar, India).
The analysis is divided into three main groups of methods:
3.1.1.2.1. Lipinski’s Rule, Ghose Filter and CMC-50-Like Rule
Lipinski's rule of five [49] (also known as Pfizer's rule) as a basic rule for the evaluation of chemical
compounds having pharmacological and/or biological activity for use as a drug for oral use. This rule is
conditional because there are over time drugs that do not cover some of its postulates.
The data from Lipinski’s rule are compared with those of the adapted Ghose Filter [50] and CMC-50-
Like Rule [51]. The data are presented in tabular form, with the corresponding color identification, showing
covering and / or exceeding requirements for each individual evaluation parameter: molecular weight (MW),
partition coefficient (logP), H-bond acceptor (HBA), H-bond donor (HBD), atom molar refractivity (AMR)
and number of atoms in the molecule (nAtom). This is necessary to more precisely clarify the genesis of the
deviations, for each indicator.
It is expected that the logP values in Ghose Filter and CMC-50-Like Rule and the molecular weight in
CMC-50-Like Rule directly reflect more on the time of penetration through the stomach wall. In cancer
patients, there is often a deviation from the normal physiology of the stomach, so it is assumed that the
deviations are not drastic and reflect more on the individual anamnesis of the patient.
3.1.1.2.2. Veber Filter, MDDR-Like Rule and BBB Likeness
Regardless of the analysis in §3.1.1.2.1. an analytically differentiable is conducted with regard to
methodologies for evaluation of medicinal products [52], based on total polar surface area (TPSA), number of
rotatable bonds (nRB), rotatable bond count (RC), number of rigid bonds (nRingidB), MW, nAcidGroup and
number of hydrogen bonds (nHB), via Weber Filter, MDDR-Like Rule and BBB Likeness.
Here, the goal is to evaluate chemical molecules by a set of variables not affected by the partition
coefficient (logP), but at the same time taking into account the influence of molecular weight (part of BBB
Likeness).
The color identification of the results specified in §3.1.1.2.1, shall be applied again in a tabular form.
The information obtained from this set of empirical rules cannot be interpreted unambiguously. These
are molecules have a larger associated volume and a total number of bonds (and hence axes and points of
rotation). Much of the molecule is occupied by a carbohydrate residue, which in most cases does not slow
down the action of the drug in the blood, simply prolongs the time spent in the stomach. Suffice it to say that
no drastic differences (in orders of magnitude) of deviations are expected.
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3.1.1.2.3. QED
The methods used in item 3.1.1.2.1. and item 3.1.1.2.2. are based on physicochemical parameters which
are considered separately. Using the Quantitative Estimate of Druglikeness (QED) methodology, an
approximation of the interchangeability of individual indicators is applied. They enter into a general linear
relationship and give a solution in the form of a scalar coefficient. This greatly facilitates the comparison of
druglikeness properties of individual molecules of a homologous order. For this purpose, other empirical and
/ or calculated variables are added: octanol-water partition coefficient (AlogP), numbers of Structural alerts
(sAlerts) and numbers of Aromatic bond count (nAromaRing).
They are two separate forms of evaluation that appear next [53]:
A. Unweighted Quantitative Estimate of Druglikeness Unweighted Quantitative Estimate of Druglikeness
(UwQED) is defined as (equation 1):
(1)
where: d is the individual desirability function, and n is the number of descriptors.
B. Weighted Quantitative Estimate of Druglikeness
Weighted Quantitative Estimate of Druglikeness (wQED) represents the functional dependence (equation 2):
(2)
where: d is the individual desirability function, w is the weight applied to each function and n is the number
of descriptors.
3.1.1.3. Conclusion from the part
Using statistical methods [54, 55] for optimization ie. statement of the task is created. It involves finding
such factor values (in this case, they overlap with the empirical results of each set of rules) in which to isolate
the most optimal dosage form suitable for conservative treatment. For this purpose, we assume that the
optimum of the objective function coincides with its extremum - minimum or maximum (by definition of the
respective rule). Here we will deliberately eliminate the statistical disturbances of the analysis - it is not
necessary to maintain chemical purity close to p.a. or higher. To avoid this difficulty, we will apply a "step-
by-step" procedure: they will be analyzed in packages according to three rules (corresponding only in terms
of their molecular weight, i.e whether they swell or not) of the two molecular structures: amide or carboxyl.
Here we do not take into account factors such as concentration, share relations, etc. quantitative variables.
In order to isolate one or at most two molecular forms, the components of the gradient are also
determined by the Box & Wilson method [56].
These results are obtained for the optimal molecular package (amide/carboxylic acid). A conclusion
should be made about druglikeness for the proposed pharmaceutical forms. It is based on a comparison of
each individual group of assays and optimally applicable molecules are derived. The final molecules were
also compared for toxicity by the Hierarchical clustering method [57] (HCM) in a T.E.S.T. [58] for Oral rat
LD50 in the form (equations 3 & 4).
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Model ellipsoid:
Rmax:
(3, 4)
Test molecule must be within ellipsoid of descriptor
values for model chemicals. The model ellipsoid
constaint is satisfied if the leverage of the test compound
(h
00
) is less than the maximum leverage value for
compounds.
Distance to the centroid of the cluster must be
less than the maximum distance for any cluster
molecule
where: Fragment constraints - Compounds in the cluster must have at least one example of each of the fragments
contained in the test molecule. Not used for binary endpoints (i.e. mutagenicity)!
T.pyriformis IGC50 (48hr), Daphnia magna LC50 (48hr) and Fathead minnow LC50 (96hr) are
relatively more accurate in terms of Coefficient of determination (R2). Oral rat LD50 and Bioaccumulation
factor are chosen because they give more general (not so profiled) results for clinical reactions, taking into
account: Predicted value and Prediction interval. Nearest neighbor (Nn) in the form: is considered as a control
sample confirming the dependence:
Three most similar molecules must exceed a minimum cosine similarity coefficient of 0.5
(5)
The neighbors are those with highest similarity coefficient. All neighbors must exceed a minimum cosine
similarity coefficient.
All coefficients, constants and other variables using a database [59, 60] of U.S. Pat. Environmental
Protection Agency. HCM are accepted as the final result for analysis and subsequent interpretation of the
results.
All values in the part are rounded to: integer for values over 10; up to a decimal value for results of
10÷1; up to hundreds of answers under 1.
3.2. Determination of the drug dose
To determine the drug dose, we need to consider all possible substances obtained by the final hydrolysis
of the glycosidic bond inside the cancer cell. For this purpose, it is necessary to calculate the concentration of
active antitumor cell forms [§6 of Article 2]. Stoichiometric calculations based on data from [§5 of Article 1]
shall be applied, using also the data on the mass ratios of amide and carboxylic acid in the preparation of a
natural precursor (in this case nitrile glycoside).
4. RESULTS
In presenting the results, tree structure in the presented methodology is strictly observed.
4.1. Analysis of data for active anticancer cell form:
To produce an active anticancer molecule inside the cancer cell, two molecular forms must be present:
an amide and a carboxylic acid. The amide molecule crosses the cell membrane and the carboxyl molecule
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minimizes the protection of the cancer cell [§5 of Article 2]. They are easily obtained from natural nitrile
glycosides [§3.2.2. of Article 1].
4.1.1. (R)-2-hydroxy-2-phenylacetamide
Subjected to analysis potential pharmaceutical forms for release within the cancer cell of (R)-2-hydroxy-
2-phenylacetamide, comprising an amides and carboxylic acids obtained by hydrolysis of the nitrile groups of
Prunasin, Amygdalin, Lucumin, Vicianin and Sambunigrin.
4.1.1.1. General Druglikeness of the pharmaceutical form
In Тable 2 are listed the values of GPCR ligand, Ion channel modulator, Kinase inhibitor, Nuclear
receptor ligand, Protease inhibitor and Enzyme inhibitor of chemical molecules potentially possible to pass
through the cancer cell membrane and release (R)-2-hydroxy-2-phenylacetamide.
Tabl. 2. Data for total druglikeness of chemical molecules potentially possible to pass through the cancer
cell membrane and release (R)-2-hydroxy-2-phenylacetamide
GPCR
ligand
Ion channel
modulator
Kinase
inhibitor
Nuclear
receptor ligand
Protease
inhibitor
Enzyme
inhibitor
Prunasin amide
0.23
-0.07
-0.05
-0.20
0.27
0.42
Prunasin acid
0.39
0.13
0.02
0.19
0.32
0.60
Amygdalin amide
0.20
-0.05
0
-0.21
0.21
0.33
Amygdalin acid
0.31
0.09
0.04
0.05
0.24
0.44
Lucumin amide
0.15
-0.07
-0.11
-0.29
0.19
0.32
Lucumin acid
0.26
0.07
-0.06
-0.01
0.22
0.44
Vicianin amide
0.15
-0,07
-0,11
-0,29
0,16
0,32
Vicianin acid
0.26
0,07
-0,06
0,01
0,22
0,44
Sambunigrin amide
0.23
-0,07
-0,05
-0,2
0,27
0,42
Sambunigrin acid
0.39
0,13
0,02
0,19
0,32
0,60
Data in Тable 2 show that the amides and carboxylic acids of Prunasin and Sambunigrin have more
pronounced overall drug activity in vivo.
4.1.1.2. Pharmacological and biological activity of oral active drugs
In Table 3 shows the empirical values (without their dimensions) for Lipinski's Rule, Ghose Filter and
CMC-50-Like Rule of chemical molecules potentially possible to pass through the cancer cell membrane and
release (R)-2-hydroxy-2-phenylacetamide.
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Tabl. 3. Lipinski's Rule, Ghose Filter and CMC-50-Like Rule of chemical molecules potentially possible to
pass through the cancer cell membrane and release (R)-2-hydroxy-2-phenylacetamide
Lipinski's Rule
Ghose Filter
CMC-50-Like Rule
MW
logP
HBA
HBD
MW
logP
AMR
nAtom
MW
logP
AMR
nAtom
Prunasin amide
313
-2.0
8
5
313
-2.0
75
41
313
-2.0
75
41
Prunasin acid
314
-1.3
8
5
314
-1.3
75
40
314
-1.3
75
40
Amygdalin amide
475
-3.5
13
8
475
-3.5
108
62
475
-3.5
108
62
Amygdalin acid
476
-2.8
13
8
476
-2.8
108
61
476
-2.8
108
61
Lucumin amide
445
-3.3
12
7
445
-3.3
102
58
445
-3.3
102
58
Lucumin acid
446
-2.6
12
7
446
-2.6
102
57
446
-2.6
102
57
Vicianin amide
445
-3.3
12
7
445
-3.3
102
58
445
-3.3
102
58
Vicianin acid
446
-2.6
12
7
446
-2.6
102
57
446
-2.6
102
57
Sambunigrin amide
313
-2.0
8
5
313
-2.0
75
41
313
-2.0
75
41
Sambunigrin acid
314
-1.3
8
5
314
-1.3
75
40
314
-1.3
75
40
Two molecular forms stand out here (the corresponding amides and carboxylic acid of Prunasin and
Sambunigrin, which cover most of the requirements. All deviations in individual indicators confirm the
preliminary conditionally accepted approximations in the methodology.
4.1.1.2.1. Veber Filter, MDDR-Like Rule and BBB Likeness
Data on Veber Filter, MDDR-Like Rule and BBB Likeness of chemical molecules potentially possible
to pass through the cancer cell membrane and release (R)-2-hydroxy-2-phenylacetamide are listed in Table 4.
Tabl. 4. Data on Veber Filter, MDDR-Like Rule and BBB Likeness of chemical molecules potentially
possible to pass through the cancer cell membrane and release (R)-2-hydroxy-2-phenylacetamide
Veber Filter
MDDR-Like Rule
BBB Likeness
TPSA
nRB
nRB
RC
nRingidB
MW
nAcidGroup
nHB
Prunasin amide
142
5
5
2
18
313
0
13
Prunasin acid
137
5
5
2
18
314
1
13
Amygdalin amide
222
8
8
3
27
475
0
21
Amygdalin acid
215
8
8
3
27
476
1
21
Lucumin amide
201
7
7
3
26
445
0
19
Lucumin acid
196
7
7
3
26
446
1
19
Vicianin amide
201
7
7
3
26
445
0
19
Vicianin acid
196
7
7
3
26
446
1
19
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Sambunigrin amide
142
5
5
2
18
313
0
13
Sambunigrin acid
136
5
5
2
18
314
1
13
There are no significant fluctuations in individual indicators. All "problematic" values correlate with the
pre-entered deviations §3.1.1.2.1.
4.1.1.3.QED
The analysis is performed according to §3.1.1.2.3.
A. uwQED rules
Data for Unweighted Quantitative Estimate of Druglikeness of the tested compounds are given in Тable.
5.
Tabl. 5. Unweighted Quantitative Estimate of Druglikeness of chemical molecules potentially possible to
pass through the cancer cell membrane and release (R)-2-hydroxy-2-phenylacetamide
uwQED
MW
AlogP
HBA
HBD
TPSA
nRB
sAlerts
nAromaRing
uwQED
Prunasin amide
313
-1.8
8
5
142
5
0
1
0,445
Prunasin acid
314
-1.4
8
5
137
5
0
1
0,475
Amygdalin amide
475
-3.5
13
8
222
8
0
1
0,123
Amygdalin acid
476
-3.1
13
8
216
8
0
1
0,133
Lucumin amide
445
-3.0
12
7
201
7
0
1
0,165
Lucumin acid
446
-2.6
12
7
196
7
0
1
0,18
Vicianin amide
445
-3.0
12
7
201
7
0
1
0,165
Vicianin acid
446
-2.6
12
7
196
7
0
1
0,18
Sambunigrin amide
313
-1.8
8
5
142
5
0
1
0,445
Sambunigrin acid
314
-1.4
8
5
137
5
0
1
0,475
The information obtained from the calculations indicates that the amides and carboxylic acids obtained
by hydrolysis of the nitrile groups of Prunasin and Sambunigrin are more applicable in a treatment.
B. wQED
In Table 6 Unweighted Quantitative Estimate of Druglikeness of chemical molecules potentially possible to
pass through the cancer cell membrane and release (R)-2-hydroxy-2-phenylacetamide.
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Tabl. 6. Weighted Quantitative Estimate of Druglikeness of chemical molecules potentially possible to pass
through the cancer cell membrane and release (R)-2-hydroxy-2-phenylacetamide
wQED
MW
AlogP
HBA
HBD
TPSA
nRB
SAlerts
nAtomRing
wQED
Prunasin amide
313
-1.8
8
5
142
5
0
1
0.52
Prunasin acid
314
-1.4
8
5
137
5
0
1
0.55
Amygdalin amide
475
-3.5
13
8
222
8
0
1
0.20
Amygdalin acid
476
-3.1
13
8
216
8
0
1
0.22
Lucumin amide
445
-3.0
12
7
201
7
0
1
0.26
Lucumin acid
446
-2.6
12
7
196
7
0
1
0.28
Vicianin amide
445
-3.0
12
7
201
7
0
1
0.26
Vicianin acid
446
-2.6
12
7
196
7
0
1
0.28
Sambunigrin amide
313
-1.8
8
5
142
5
0
1
0.52
Sambunigrin acid
314
-1.4
8
5
137
5
0
1
0.55
The information obtained from the calculations indicates the amides and carboxylic acids of Prunasin
and Sambunigrin as covering the requirements for Weighted Quantitative Estimate of Druglikeness.
4.1.1.4. Conclusion from the part
The application of the methodological scheme from §3.1.1.3 for a potential pharmacological form
(§4.1.1), proves maximum qualification for oral medicinal products. No toxicity deviations were observed and
the values were respectively: Oral rat LD50 [mg/kg] for Prunasin amide and Sambunigrin amide 2229 ≤ 5588
≤ 14008, Prunasin acid and Sambunigrin acid 1904 ≤ 5178 ≤ 14079 and Bioaccumulation factor [conditional
units] Prunasin amide and Sambunigrin amide 1.03 ≤ 16 ≤ 255.9, Prunasin acid and Sambunigrin acid are 0.00
≤ 0.30 ≤ 617; 0.05 ≤ 0.39 ≤ 3.2. This is understandable because both compounds are in isomeric form.
4.1.2. (R)-2-hydroxy-2-(4-hydroxyphenyl)acetamide
Subjected to analysis are potential pharmaceutical forms for release within the cancer cell of (R)-2-
hydroxy-2-(4-hydroxyphenyl)acetamide, comprising an amides and carboxylic acids obtained by hydrolysis
of the nitrile groups of Dhurrin, Taxiphyllin, Proteacin and p-Glucosyloxymandelin.
4.1.2.1. Druglikeness of the pharmaceutical form
In Тable 7 are listed values of GPCR ligand, Ion channel modulator, Kinase inhibitor, Nuclear receptor
ligand, Protease inhibitor and Enzyme inhibitor of chemical molecules potentially possible to pass through
the cancer cell membrane and release (R)-2-hydroxy-2-(4-hydroxyphenyl)acetamide.
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Tabl. 7. Data for total druglikeness of chemical molecules potentially possible to pass through the cancer
cell membrane and release (R)-2-hydroxy-2-(4-hydroxyphenyl)acetamide
GPCR
ligand
Ion channel
modulator
Kinase
inhibitor
Nuclear receptor
ligand
Protease
inhibitor
Enzyme
inhibitor
Dhurrin amide
0.27
-0.04
0.01
-0.05
0.28
0.44
Dhurrin acid
0.42
0.16
0.07
0.33
0.32
0.61
Taxiphyllin amide
0.27
-0.04
0.01
-0.05
0.28
0.44
Taxiphyllin acid
0.42
0.16
0.07
0.33
0.32
0.61
Proteacin amide
0.14
-0.08
-0.08
-0.11
0.17
0.29
Proteacin acid
0.24
0.05
-0.04
0.14
0.20
0.41
p-Glucosyloxymandelo- amide
0.13
-0.11
-0.08
-0.06
0.14
0.39
p-Glucosyloxymandelo- acid
0.29
0.02
-0.05
0.32
0.17
0.45
The data in Table 7 show that the amides and carboxylic acids of Dhurrin and Taxiphyllin have more
pronounced general drug activity in vivo.
4.1.2.2. Pharmacological and biological activity of oral active drugs
4.1.2.2.1. Lipinski’s Rule, Ghose Filter and CMC-50-Like Rule
In Table 8 shows the empirical values (without their dimensions) for Lipinski's Rule, Ghose Filter and
CMC-50-Like Rule of chemical molecules potentially possible to pass through the cancer cell membrane and
release (R)-2-hydroxy-2-(4-hydroxyphenyl)acetamide.
Tabl. 8. Lipinski's Rule, Ghose Filter and CMC-50-Like Rule of chemical molecules potentially possible to
pass through the cancer cell membrane and release (R)-2-hydroxy-2-(4-hydroxyphenyl)acetamide
Lipinski's Rule
Ghose Filter
CMC-50-Like Rule
MW
logP
HBA
HBD
MW
logP
AMR
nAtom
MW
logP
AMR
nAtom
Dhurrin amide
329
-2.7
9
6
329
-2.7
77
42
329
-2.7
77
42
Dhurrin acid
330
-2.0
9
6
330
-2.0
77
41
330
-2.0
77
41
Taxiphyllin amide
329
-2,7
9
6
329
-2.7
77
42
329
-2.7
77
42
Taxiphyllin acid
330
-2.0
9
6
330
-2.0
77
41
330
-2.0
77
41
Proteacin amide
491
-4.0
14
9
491
-4.0
110
63
491
-4.0
110
63
Proteacin acid
492
-3.3
14
9
492
-3.3
110
62
492
-3.3
110
62
p-Glucosyloxymandelo- amide
329
-2.9
9
6
329
-2.9
77
42
329
-2.9
77
42
p-Glucosyloxymandelo- acid
330
-2.2
9
6
330
-2.2
77
41
330
-2.2
77
41
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Here there are two molecular forms that stand out (the respective amides and carboxylic acid of Dhurrin
and Taxiphyllin which cover most of the requirements. All deviations in individual indicators confirm the
preliminary conditionally accepted approximations in the methodology.
4.1.2.2.2. Veber Filter, MDDR-Like Rule and BBB Likeness
Data on Veber Filter, MDDR-Like Rule and BBB Likeness of chemical molecules potentially possible
to pass through the cancer cell membrane and release (R)-2-hydroxy-2-(4-hydroxyphenyl)acetamide are listed
in Table 9.
Tabl. 9. Data on Veber Filter, MDDR-Like Rule and BBB Likeness of chemical molecules potentially
possible to pass through the cancer cell membrane and release (R)-2-hydroxy-2-(4-
hydroxyphenyl)acetamide
Veber Filter
MDDR-Like Rule
BBB Likeness
TPSA
nRB
nRB
RC
nRingidB
MW
nAcidGroup
nHB
Dhurrin amide
167
5
5
2
19
329
0
15
Dhurrin acid
157
5
5
2
19
330
1
15
Taxiphyllin amide
163
5
5
2
19
329
0
15
Taxiphyllin acid
157
5
5
2
19
330
1
15
Proteacin amide
242
8
8
3
28
491
0
23
Proteacin acid
236
8
8
3
28
492
1
23
p-Glucosyloxymandelo- amide
163
5
5
2
19
329
0
15
p-Glucosyloxymandelo- acid
157
5
5
2
19
330
1
15
There are no significant fluctuations in individual indicators. All "problematic" values correlate with the
pre-entered deviations §3.1.1.2.1.
4.1.2.2.3. QED
The analysis is performed according to §3.1.1.2.3.
A. uwQED
Data for Unweighted Quantitative Estimate of Druglikeness of the tested compounds are given in Table.
10.
Tabl. 10. Unweighted Quantitative Estimate of Druglikeness of chemical molecules potentially possible to
pass through the cancer cell membrane and release (R)-2-hydroxy-2-(4-hydroxyphenyl)acetamide
uwQED
MW
AlogP
HBA
HBD
TPSA
nRB
SAlerts
nAromaRing
uwQED
Dhurrin amide
329
-2.4
9
6
163
5
0
1
0.32
Dhurrin acid
330
-2.0
9
6
157
5
0
1
0.35
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Taxiphyllin amide
329
-2.4
9
6
163
5
0
1
0.32
Taxiphyllin acid
330
-2.0
9
6
157
5
0
1
0.35
Proteacin amide
491
-4.4
14
9
242
8
0
1
0.10
Proteacin acid
492
-4.0
14
9
236
8
0
1
0.15
p-Glucosyloxymandeloamide
329
-2.7
9
6
163
5
0
1
0.30
p-Glucosyloxymandelo acid
330
-2.3
9
6
157
5
0
1
0.33
The information obtained from the calculations indicates that the amides and carboxylic acids of the
studied molecules to the same extent deviate from the defined rules. In the absolute approximation, Dhurrin
and Taxiphyllin derivatives would be more applicable for treatment.
B. wQED
In Table 11 Unweighted Quantitative Estimate of Druglikeness of chemical molecules potentially
possible to pass through the cancer cell membrane and release (R)-2-hydroxy-2-(4-hydroxyphenyl)acetamide
Tabl. 11. Weighted Quantitative Estimate of Druglikeness of chemical molecules potentially possible to pass
through the cancer cell membrane and release (R)-2-hydroxy-2-(4-hydroxyphenyl)acetamide
wQED
MW
AlogP
HBA
HBD
TPSA
nRB
SAlerts
nAtomRing
wQED
Dhurrin amide
329
-2.4
9
6
163
5
0
1
0.41
Dhurrin acid
330
-2.0
9
6
157
5
0
1
0.44
Taxiphyllin amide
329
-2.4
9
6
163
5
0
1
0.41
Taxiphyllin acid
330
-2.0
9
6
157
5
0
1
0.44
Proteacin amide
491
-4.4
14
9
242
8
0
1
0.17
Proteacin acid
492
-4.0
14
9
236
8
0
1
0.18
p-Glucosyloxymandelo amide
329
-2.7
9
6
163
5
0
1
0.39
p-Glucosyloxymandelo acid
330
-2.3
9
6
157
5
0
1
0.42
uwQED (Tabl.10) and wQED (Tabl.11) of potential pharmaceutical forms including amides and
carboxylic acids obtained by hydrolysis of the nitrile group of Dhurrin, Taxiphyllin, Proteacin and p-
Glucosyloxymandelamin meet the requirements for conservative treatment.
4.1.2.3.Conclusion from the part
The application of the methodological scheme from §3.1.1.3 for a potential pharmacological form
(§4.1.2), proves maximum qualification for oral medicinal products. No toxicity deviations were observed and
the values were respectively: Oral rat LD50 [mg/kg] for Dhurrin amide and Taxiphyllin amide 2541 ≤ 7077
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≤ 19709, Dhurrin acid and Taxiphyllin acid 1159 ≤ 2970 ≤ 7612 and Bioaccumulation factor [conditional
units] Dhurrin amide and Taxiphyllin amide 1.1 ≤ 17 ≤ 272, Dhurrin acid and Taxiphyllin acid are 0.01 ≤ 0.28
≤ 6.1. This is understandable because both compounds are in isomeric form.
4.1.3. (R)-2-hydroxy-2-(3-hydroxyphenyl)acetamide
Subjected to analysis potential pharmaceutical form for release within the cancer cell of (R)-2-hydroxy-
2-(3-hydroxyphenyl)acetamide, comprising an amide and a carboxylic acid obtained by hydrolysis of the
nitrile group of Zierin.
4.1.3.1. Druglikeness of the pharmaceutical form
In Тable 12 are listed values of GPCR ligand, Ion channel modulator, Kinase inhibitor, Nuclear receptor
ligand, Protease inhibitor and Enzyme inhibitor of chemical molecules potentially possible to pass through
the cancer cell membrane and release (R)-2-hydroxy-2-(3-hydroxyphenyl)acetamide.
Tabl. 12. Data for total druglikeness of chemical molecules potentially possible to pass through the cancer
cell membrane and release (R)-2-hydroxy-2-(3-hydroxyphenyl)acetamide
GPCR
ligand
Ion channel modulator
Kinase
inhibitor
Nuclear receptor
ligand
Protease
inhibitor
Enzyme
inhibitor
Zierin amide
0.26
-0.05
-0.01
-0.04
0.27
0.44
Zierin acid
0.41
0.15
0.05
0.33
0.31
0.61
Data in Тabl.12 show that the amides and carboxylic acids of Zierin have more pronounced overall drug
activity in vivo.
4.1.3.2. Pharmacological and biological activity of oral active drugs
4.1.3.2.1. Lipinski’s Rule, Ghose Filter and CMC-50-Like Rule
In Table 13 shows the empirical values (without their dimensions) for Lipinski's Rule, Ghose Filter and
CMC-50-Like Rule of chemical molecules potentially possible to pass through the cancer cell membrane and
release (R)-2-hydroxy-2-(3-hydroxyphenyl)acetamide.
Tabl. 13. Lipinski's Rule, Ghose Filter and CMC-50-Like Rule of chemical molecules potentially possible to
pass through the cancer cell membrane and release (R)-2-hydroxy-2-(3-hydroxyphenyl)acetamide
Lipinski's Rule
Ghose Filter
CMC-50-Like Rule
MW
logP
HBA
HBD
MW
logP
AMR
nAtom
MW
logP
AMR
nAtom
Zierin amide
329
-2.7
9
6
329
-2.7
77
42
329
-2.7
77
42
Zierin acid
330
-2.0
9
6
330
-2.0
77
41
330
-2.0
77
41
The two molecular modified forms of Zierin cover most of the requirements. All deviations in individual
indicators confirm the preliminary conditionally accepted approximations in the methodology.
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4.1.3.2.2. Veber Filter, MDDR-Like Rule and BBB Likeness
Data on Veber Filter, MDDR-Like Rule and BBB Likeness of chemical molecules potentially possible
to pass through the cancer cell membrane and release (R)-2-hydroxy-2-(3-hydroxyphenyl)acetamide are listed
in Table 14.
Tabl. 14. Data on Veber Filter, MDDR-Like Rule and BBB Likeness of chemical molecules potentially
possible to pass through the cancer cell membrane and release (R)-2-hydroxy-2-(3-
hydroxyphenyl)acetamide
Veber Filter
MDDR-Like Rule
BBB Likeness
TPSA
nRB
nRB
RC
nRingidB
MW
nAcidGroup
nHB
Zierin amide
163
5
5
2
19
329
0
15
Zierin acid
157
5
5
2
19
330
1
15
a.
There are no significant fluctuations in the individual indicators. All "problematic" values correlate with
the pre-entered deviations §3.1.1.2.1.
4.1.3.2.3. QED
The analysis is performed according to §3.1.1.2.3.
A. uwQED
Data for Unweighted Quantitative Estimate of Druglikeness of the tested compounds are given in Table
15.
Tabl. 15. Unweighted Quantitative Estimate of Druglikeness of chemical molecules potentially possible to
pass through the cancer cell membrane and release (R)-2-hydroxy-2-(3-hydroxyphenyl)acetamide
uwQED
MW
AlogP
HBA
HBD
TPSA
nRB
sAlerts
nAromaRing
uwQED
Zierin amide
329
-2.4
9
6
163
5
0
1
0.32
Zierin acid
330
-2.0
9
6
157
5
0
1
0.35
B. wQED
In Table 16 Unweighted Quantitative Estimate of Druglikeness of chemical molecules potentially
possible to pass through the cancer cell membrane and release (R)-2-hydroxy-2-(3-hydroxyphenyl)acetamide.
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Tabl. 16. Weighted Quantitative Estimate of Druglikeness of chemical molecules potentially possible to pass
through the cancer cell membrane and release (R)-2-hydroxy-2-(3-hydroxyphenyl)acetamide
wQED
MW
AlogP
HBA
HBD
TPSA
nRB
SAlerts
nAtomRing
wQED
Zierin amide
329
-2.4
9
6
163
5
0
1
0.41
Zierin acid
330
-2.0
9
6
157
5
0
1
0.44
uwQED (Tabl.15) and wQED (Tabl.16) of a potential pharmaceutical form including amide and
carboxylic acid obtained by hydrolysis of the nitrile group of Zierin meets the requirements for conservative
treatment.
4.1.3.3. Conclusion from the part
The application of the methodological scheme from §3.1.1.3 for a potential pharmacological form
(§4.1.3), proves maximum qualification for oral medicinal products. No toxicity deviations were observed and
the values were respectively: Oral rat LD50 [mg/kg] for amide 2646 ≤ 7387 ≤ 20621, acid 2283 ≤ 5725 ≤
14356 и Bioaccumulation factor [conditional units] amide 1.1 ≤ 18 ≤ 279, acid 0.03 ≤ 0.64 ≤ 14.
4.1.4. 2-hydroxy-2-methylpropanamide
Subject to analysis is a potential pharmaceutical form for release within the cancer cell of 2-hydroxy-2-
methylpropanamide, comprising an amide and a carboxylic acid obtained by hydrolysis of the nitrile group of
Linamarin.
4.1.4.1. Druglikeness of the pharmaceutical form
In Тable 17 are listed values of GPCR ligand, Ion channel modulator, Kinase inhibitor, Nuclear receptor
ligand, Protease inhibitor and Enzyme inhibitor of chemical molecules potentially possible to pass through
the cancer cell membrane and release 2-hydroxy-2-methylpropanamide.
Tabl. 17. Data for total druglikeness of chemical molecules potentially possible to pass through the cancer
cell membrane and release 2-hydroxy-2-methylpropanamide
GPCR
ligand
Ion channel
modulator
Kinase
inhibitor
Nuclear receptor
ligand
Protease
inhibitor
Enzyme
inhibitor
Linamarin amide
0.15
0.18
0
-0,20
0.19
0.57
Linamarin acid
0.22
0.20
-0.13
0.28
0.09
0.75
Data in Тabl.17 show that the amides and carboxylic acids of Linamarin have more pronounced overall
drug activity in vivo.
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4.1.4.2.Pharmacological and biological activity of oral active drugs
4.1.4.2.1. Lipinski’s Rule, Ghose Filter and CMC-50-Like Rule
In Table 18 shows the empirical values (without their dimensions) for Lipinski's Rule, Ghose Filter and
CMC-50-Like Rule of chemical molecules potentially possible to pass through the cancer cell membrane and
release 2-hydroxy-2-methylpropanamide.
Tabl. 18. Lipinski's Rule, Ghose Filter and CMC-50-Like Rule of chemical molecules potentially possible to
pass through the cancer cell membrane and release 2-hydroxy-2-methylpropanamide
Lipinski's Rule
Ghose Filter
CMC-50-Like Rule
MW
logP
HBA
HBD
MW
logP
AMR
nAtom
MW
logP
AMR
nAtom
Linamarin amide
265
-2.3
8
5
265
-2.3
56
37
265
-2.3
56
37
Linamarin acid
266
-1.6
8
5
266
-1.6
56
36
266
-1.6
56
36
The two molecular modified forms of Linamarin meet most requirements. All deviations in individual
indicators confirm the preliminary conditionally accepted approximations in the methodology.
4.1.4.2.2. Veber Filter, MDDR-Like Rule and BBB Likeness
Data on Veber Filter, MDDR-Like Rule and BBB Likeness of chemical molecules potentially possible
to pass through the cancer cell membrane and release 2-hydroxy-2-methylpropanamide are listed in Table 19.
Tabl. 19. Data on Veber Filter, MDDR-Like Rule and BBB Likeness of chemical molecules potentially
possible to pass through the cancer cell membrane and release 2-hydroxy-2-methylpropanamide
Veber Filter
MDDR-Like Rule
BBB Likeness
TPSA
nRB
nRB
RC
nRingidB
MW
nAcidGroup
nHB
Linamarin amide
142
4
4
1
14
265
0
13
Linamarin acid
137
4
4
1
14
266
1
13
There are no significant fluctuations in individual indicators. All "problematic" values correlate with the
pre-entered deviations §3.1.1.2.1.
4.1.4.2.3. QED
The analysis is performed according to §3.1.1.2.3.
A. uwQED
Data for Unweighted Quantitative Estimate of Druglikeness of the tested compounds are given in Table
20.
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Tabl. 20. Unweighted Quantitative Estimate of Druglikeness of chemical molecules potentially possible to
pass through the cancer cell membrane and release 2-hydroxy-2-methylpropanamide
uwQED
MW
AlogP
HBA
HBD
TPSA
nRB
SAlerts
nAromaRing
uwQED
Linamarin amide
265
-2.2
8
5
142
4
0
0
0.38
Linamarin acid
266
-1.8
8
5
137
4
0
0
0.41
B. wQED
In Table 21 Unweighted Quantitative Estimate of Druglikeness of chemical molecules potentially
possible to pass through the cancer cell membrane and release 2-hydroxy-2-methylpropanamide
Tabl. 21. Weighted Quantitative Estimate of Druglikeness of chemical molecules potentially possible to pass
through the cancer cell membrane and release 2-hydroxy-2-methylpropanamide
wQED
MW
AlogP
HBA
HBD
TPSA
nRB
Salerts
nAtomRing
wQED
Linamarin amide
265
-2.2
8
5
142
4
0
0
0.45
Linamarin acid
266
-1.8
8
5
137
4
0
0
0.47
uwQED (Table 20) and wQED (Table 21) of a potential pharmaceutical form including amide and
carboxylic acid obtained by hydrolysis of the nitrile group of Linamarin meets the requirements for
conservative treatment.
4.1.4.3. Conclusion from the part
The application of the methodological scheme from §3.1.1.3 for a potential pharmacological form
(§4.1.4), proves maximum qualify for oral medicinal products. No toxicity deviations were observed and the
values were respectively: Oral rat LD50 [mg/kg] for amide 1092 ≤ 2219 ≤ 4507, acid 1218 ≤ 2280 ≤ 4266 and
Bioaccumulation factor [conditional units] amide 0.02 ≤ 18 ≤ 13516, acid 0.24 ≤ 1.2 ≤ 6,2.
4.1.5. (S)-2-hydroxy-2-methylbutanamide
Subject to analysis is a potential pharmaceutical form for release within the cancer cell of (S)-2-hydroxy-
2-methylbutanamide, comprising an amide and a carboxylic acid obtained by hydrolysis of the nitrile group
of Lotaustralin.
4.1.5.1.Druglikeness of the pharmaceutical form
In Тable 22 are listed values of GPCR ligand, Ion channel modulator, Kinase inhibitor, Nuclear receptor
ligand, Protease inhibitor and Enzyme inhibitor of chemical molecules potentially possible to pass through
the cancer cell membrane and release (R)-2-hydroxy-2-(3-hydroxyphenyl)acetamide.
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Tabl. 22. Data for total druglikeness of chemical molecules potentially possible to pass through the cancer
cell membrane and release (R)-2-hydroxy-2-(3-hydroxyphenyl)acetamide
GPCR
ligand
Ion channel
modulator
Kinase
inhibitor
Nuclear receptor
ligand
Protease
inhibitor
Enzyme
inhibitor
Lotaustralin amide
0.14
0.14
0
-0.60
0.24
0.58
Lotaustralin acid
0.20
0.16
-0.12
0.31
0.15
0.75
Data in Тabl.22 show that the amides and carboxylic acids of Lotaustralin have more pronounced overall
drug activity in vivo.
4.1.5.2.Pharmacological and biological activity of oral active drugs
4.1.5.2.1. Lipinski’s Rule, Ghose Filter and CMC-50-Like Rule
In Table 23 shows the empirical values (without their dimensions) for Lipinski's Rule, Ghose Filter and
CMC-50-Like Rule of chemical molecules potentially possible to pass through the cancer cell membrane and
release (S)-2-hydroxy-2-methylbutanamide.
Tabl. 23. Lipinski's Rule, Ghose Filter and CMC-50-Like Rule of chemical molecules potentially possible to
pass through the cancer cell membrane and release (S)-2-hydroxy-2-methylbutanamide
Lipinski's Rule
Ghose Filter
CMC-50-Like Rule
MW
logP
HBA
HBD
MW
logP
AMR
nAtom
MW
logP
AMR
nAtom
Lotaustralin amide
279
-2.0
8
5
279
-2.0
59
40
279
-2.0
59
40
Lotaustralin acid
280
-1.2
8
5
280
-1.2
59
39
280
-1.2
59
39
The two molecular modified forms of Lotaustralin meet most requirements. All deviations in individual
indicators confirm the preliminary conditionally accepted approximations in the methodology.
4.1.5.2.2. Veber Filter, MDDR-Like Rule and BBB Likeness
Data on Veber Filter, MDDR-Like Rule and BBB Likeness of chemical molecules potentially possible
to pass through the cancer cell membrane and release (S)-2-hydroxy-2-methylbutanamide are listed in Table
24.
Tabl. 24. Data on Veber Filter, MDDR-Like Rule and BBB Likeness of chemical molecules potentially
possible to pass through the cancer cell membrane and release (S)-2-hydroxy-2-methylbutanamide
Veber Filter
MDDR-Like Rule
BBB Likeness
TPSA
nRB
nRB
RC
nRingidB
MW
nAcidGroup
nHB
Lotaustralin amide
142
5
5
1
14
279
0
13
Lotaustralin acid
137
5
5
1
14
280
1
13
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There are no significant fluctuations in individual indicators. All "problematic" values correlate with the
pre-entered deviations §3.1.1.2.1.
4.1.5.2.3. QED
The analysis is performed according to §3.1.1.2.3.
A. uwQED
Data for Unweighted Quantitative Estimate of Druglikeness of the tested compounds are given in Table
25.
Tabl. 25. Unweighted Quantitative Estimate of Druglikeness of chemical molecules potentially possible to
pass through the cancer cell membrane and release (S)-2-hydroxy-2-methylbutanamide
uwQED
MW
AlogP
HBA
HBD
TPSA
nRB
sAlerts
nAromaRing
uwQED
Lotaustralin amide
279
-2.9
8
5
142
5
0
0
0.34
Lotaustralin acid
280
-2.5
8
5
137
5
0
0
0.37
B. wQED
In Table 26 Unweighted Quantitative Estimate of Druglikeness of chemical molecules potentially
possible to pass through the cancer cell membrane and release (S)-2-hydroxy-2-methylbutanamide
Tabl. 26. Weighted Quantitative Estimate of Druglikeness of chemical molecules potentially possible to pass
through the cancer cell membrane and release (S)-2-hydroxy-2-methylbutanamide
wQED
MW
AlogP
HBA
HBD
TPSA
nRB
SAlerts
nAtomRing
wQED
Lotaustralin amide
279
-2.9
8
5
142
5
0
0
0.40
Lotaustralin acid
280
-2.5
8
5
137
5
0
0
0.43
uwQED (Tabl.25) and wQED (Tabl.26) of a potential pharmaceutical form including amide and
carboxylic acid obtained by hydrolysis of the nitrile group of Lotaustralin meets the requirements for
conservative treatment.
4.1.5.3. Conclusion from the part
The application of the methodological scheme from §3.1.1.3 for a potential pharmacological form
(§4.1.5), proves maximum qualification for oral medicinal products. No toxicity deviations were observed and
the values were respectively: Oral rat LD50 [mg/kg] for amide 3000 ≤ 8420 ≤ 23633, acid 5279 ≤ 13466 ≤
34351 и Bioaccumulation factor [conditional units] amide 4.0 ≤ 65 ≤ 1043, acid 0.04 ≤ 0.34 ≤ 3.0.
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4.1.6. 2-hydroxy-3-methylbut-2-enamide
Subjected to analysis potential pharmaceutical form for release within the cancer cell of 2-hydroxy-3-
methylbut-2-enamide, comprising an amide and a carboxylic acid obtained by hydrolysis of the nitrile group
of Acacipetalin.
Druglikeness of the pharmaceutical form
In Тable 27 are listed values of GPCR ligand, Ion channel modulator, Kinase inhibitor, Nuclear receptor
ligand, Protease inhibitor and Enzyme inhibitor of chemical molecules potentially possible to pass through
the cancer cell membrane and release 2-hydroxy-3-methylbut-2-enamide.
Tabl. 27. Data for total druglikeness of chemical molecules potentially possible to pass through the cancer
cell membrane and release 2-hydroxy-3-methylbut-2-enamide
GPCR
ligand
Ion channel
modulator
Kinase
inhibitor
Nuclear receptor
ligand
Protease
inhibitor
Enzyme
inhibitor
Acacipetalin amide
0.11
0.08
-0.17
-0.21
0.08
0.58
Acacipetalin acid
0.25
0.14
-0.25
-0.02
0.03
0.75
Data in Тabl.27 show that the amides and carboxylic acids of Acacipetalin have more pronounced
overall drug activity in vivo.
4.1.6.1.Pharmacological and biological activity of oral active drugs
4.1.6.1.1. Lipinski’s Rule, Ghose Filter and CMC-50-Like Rule
In Table 28 shows the empirical values (without their dimensions) for Lipinski's Rule, Ghose Filter and
CMC-50-Like Rule of chemical molecules potentially possible to pass through the cancer cell membrane and
release 2-hydroxy-3-methylbut-2-enamide.
Tabl. 28. Lipinski's Rule, Ghose Filter and CMC-50-Like Rule of chemical molecules potentially possible to
pass through the cancer cell membrane and release 2-hydroxy-3-methylbut-2-enamide
Lipinski's Rule
Ghose Filter
CMC-50-Like Rule
MW
logP
HBA
HBD
MW
logP
AMR
nAtom
MW
logP
AMR
nAtom
Acacipetalin amide
277
-1.7
8
5
277
-1.7
62
38
277
-1.7
62
38
Acacipetalin acid
278
-1.0
8
5
278
-1.0
62
37
278
-1.0
62
37
The two molecular modified forms of Acacipetalin meet most requirements. All deviations in individual
indicators confirm the preliminary conditionally accepted approximations in the methodology.
4.1.6.1.2. Veber Filter, MDDR-Like Rule and BBB Likeness
Data on Veber Filter, MDDR-Like Rule and BBB Likeness of chemical molecules potentially possible
to pass through the cancer cell membrane and release 2-hydroxy-3-methylbut-2-enamide are listed in Table
29.
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Tabl. 29. Data on Veber Filter, MDDR-Like Rule and BBB Likeness of chemical molecules potentially
possible to pass through the cancer cell membrane and release 2-hydroxy-3-methylbut-2-enamide
Veber Filter
MDDR-Like Rule
BBB Likeness
TPSA
nRB
nRB
RC
nRingidB
MW
nAcidGroup
nHB
Acacipetalin amide
142
4
4
1
15
277
0
13
Acacipetalin acid
137
4
4
1
15
278
1
13
There are no significant fluctuations in individual indicators. All "problematic" values correlate with the
pre-entered deviations §3.1.1.2.1.
4.1.6.1.3. QED
The analysis is performed according to §3.1.1.2.3.
A. uwQED
Data for Unweighted Quantitative Estimate of Druglikeness of the tested compounds are given in Table
30.
Tabl. 30. Unweighted Quantitative Estimate of Druglikeness of chemical molecules potentially possible to
pass through the cancer cell membrane and release 2-hydroxy-3-methylbut-2-enamide
uwQED
MW
AlogP
HBA
HBD
TPSA
nRB
sAlerts
nAromaRing
uwQED
Acacipetalin amide
277
-1.7
8
5
142
4
2
0
0.39
Acacipetalin acid
278
-1.3
8
5
137
4
2
0
0.41
B. wQED
In Table 31 presents the data from the calculations for a Weighted Quantitative Estimate of Druglikeness
of chemical molecules potentially possible to pass through the cancer cell membrane and release 2-hydroxy-
3-methylbut-2-enamide.
Tabl. 31. Weighted Quantitative Estimate of Druglikeness of chemical molecules potentially possible to pass
through the cancer cell membrane and release 2-hydroxy-3-methylbut-2-enamide
wQED
MW
AlogP
HBA
HBD
TPSA
nRB
SAlerts
nAtomRing
wQED
Acacipetalin amide
277
-1.7
8
5
142
4
2
0
0.42
Acacipetalin acid
278
-1.3
8
5
137
4
2
0
0.44
uwQED (Table 30) and wQED (Table 31) of a potential pharmaceutical form including amide and
carboxylic acid obtained by hydrolysis of the nitrile group of Acacipetalin meets the requirements for
conservative treatment.
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4.1.6.2.Conclusion from the part
The application of the methodological scheme from §3.1.1.3 for a potential pharmacological form
(§4.1.6), proves maximum qualification for oral medicinal products. No toxicity deviations were observed and
the values were respectively: Oral rat LD50 [mg/kg] for amide 4475 ≤ 11299 ≤ 28525, acid 5246 ≤ 13299 ≤
33715 и Bioaccumulation factor [conditional units] amide 2.45 ≤ 39 ≤ 637, acid 0,02 ≤ 0.17 ≤ 1.5.
4.1.7. (2Z,4E)-4-(2-amino-1-hydroxy-2-oxoethylidene)hex-2-enedioic acid
Subjected to analysis potential pharmaceutical form for release within the cancer cell of (2Z,4E)-4-(2-
amino-1-hydroxy-2-oxoethylidene)hex-2-enedioic acid, comprising an amide and a carboxylic acid obtained
by hydrolysis of the nitrile group of Triglochinin.
4.1.7.1.Druglikeness of the pharmaceutical form
In Тable 32 are listed values of GPCR ligand, Ion channel modulator, Kinase inhibitor, Nuclear
receptor ligand, Protease inhibitor and Enzyme inhibitor of chemical molecules potentially possible to pass
through the cancer cell membrane and release (2Z,4E)-4-(2-amino-1-hydroxy-2-oxoethylidene)hex-2-
enedioic acid.
Tabl. 32. Data for total druglikeness of chemical molecules potentially possible to pass through the cancer
cell membrane and release (2Z,4E)-4-(2-amino-1-hydroxy-2-oxoethylidene)hex-2-enedioic acid
GPCR
ligand
Ion channel
modulator
Kinase
inhibitor
Nuclear receptor
ligand
Protease
inhibitor
Enzyme
inhibitor
Triglochinin amide
0.37
0.10
-0.10
0.22
0.27
0.56
Triglochinin acid
0.40
0.12
-0.12
0.28
0.18
0.64
Data in Тable 32 show that the amides and carboxylic acids of Triglochinin have more pronounced
overall drug activity in vivo.
4.1.7.2. Pharmacological and biological activity of oral active drugs
4.1.7.2.1. Lipinski’s Rule, Ghose Filter and CMC-50-Like Rule
In Table 33 shows the empirical values (without their dimensions) for Lipinski's Rule, Ghose Filter and
CMC-50-Like Rule of chemical molecules potentially possible to pass through the cancer cell membrane and
release (2Z,4E)-4-(2-amino-1-hydroxy-2-oxoethylidene)hex-2-enedioic acid.
Tabl. 33. Lipinski's Rule, Ghose Filter and CMC-50-Like Rule of chemical molecules potentially possible to
pass through the cancer cell membrane and release (2Z,4E)-4-(2-amino-1-hydroxy-2-oxoethylidene)hex-2-
enedioic acid
Lipinski's Rule
Ghose Filter
CMC-50-Like Rule
MW
logP
HBA
HBD
MW
logP
AMR
nAtom
MW
logP
AMR
nAtom
Triglochinin amide
377
-2.9
12
7
377
-2.9
80
45
377
-2.9
80
45
Triglochinin acid
378
-2.1
12
7
378
-2.1
80
44
378
-2.1
80
44
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The two molecular modified forms of Triglochinin meet most requirements. All deviations in individual
indicators confirm the preliminary conditionally accepted approximations in the methodology.
4.1.7.2.2. Veber Filter, MDDR-Like Rule and BBB Likeness
Data on Veber Filter, MDDR-Like Rule and BBB Likeness of chemical molecules potentially possible
to pass through the cancer cell membrane and release (2Z,4E)-4-(2-amino-1-hydroxy-2-oxoethylidene)hex-2-
enedioic acid are listed in Table 34.
Tabl. 34. Data on Veber Filter, MDDR-Like Rule and BBB Likeness of chemical molecules potentially
possible to pass through the cancer cell membrane and release (2Z,4E)-4-(2-amino-1-hydroxy-2-
oxoethylidene)hex-2-enedioic acid
Veber Filter
MDDR-Like Rule
BBB Likeness
TPSA
nRB
nRB
RC
nRingidB
MW
nAcidGroup
nHB
Triglochinin amide
217
8
8
1
18
377
2
19
Triglochinin acid
211
8
8
1
18
378
3
19
There are no significant fluctuations in individual indicators. All "problematic" values correlate with the
pre-entered deviations §3.1.1.2.1.
4.1.7.2.3. QED
The analysis is performed according to §3.1.1.2.3.
A. uwQED
Data for Unweighted Quantitative Estimate of Druglikeness of the tested compounds are given in Table
35.
Tabl. 35. Unweighted Quantitative Estimate of Druglikeness of chemical molecules potentially possible to
pass through the cancer cell membrane and release (2Z,4E)-4-(2-amino-1-hydroxy-2-oxoethylidene)hex-2-
enedioic acid
uwQED
MW
AlogP
HBA
HBD
TPSA
nRB
sAlerts
nAromaRing
uwQED
Triglochinin amide
377
-3.1
12
7
217
8
3
0
0.13
Triglochinin acid
378
-2.7
12
7
211
8
3
0
0.14
B. wQED
In Table 36 presents the data from the calculations for a Weighted Quantitative Estimate of Druglikeness of
chemical molecules potentially possible to pass through the cancer cell membrane and release (2Z,4E)-4-(2-
amino-1-hydroxy-2-oxoethylidene)hex-2-enedioic acid.
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Tabl. 36. Weighted Quantitative Estimate of Druglikeness of chemical molecules potentially possible to pass
through the cancer cell membrane and release (2Z,4E)-4-(2-amino-1-hydroxy-2-oxoethylidene)hex-2-
enedioic acid
wQED
MW
AlogP
HBA
HBD
TPSA
nRB
SAlerts
nAtomRing
wQED
Triglochinin amide
277
-3.1
12
7
217
8
3
0
0.18
Triglochinin acid
378
-2.7
12
7
211
8
3
0
0.19
uwQED (Table 35) and wQED (Table 36) of a potential pharmaceutical form including amide and
carboxylic acid obtained by hydrolysis of the nitrile group of Triglochinin meets the requirements for
conservative treatment.
4.1.7.3. Conclusion from the part
The application of the methodological scheme from §3.1.1.3 for a potential pharmacological form
(§4.1.7), proves maximum qualification for oral medicinal products. No toxicity deviations were observed and
the values were respectively: Oral rat LD50 [mg/kg] for amide 4809 ≤ 13902 ≤ 40189, acid 3803 ≤ 9795 ≤
25227 и Bioaccumulation factor [conditional units] amide 0.00 ≤ 2.28E-02 ≤ 0.57, acid are values close to 0.
4.1.8. (S)-1-hydroxycyclopent-2-ene-1-carboxamide
Subject to analysis are potential pharmaceutical forms for release within the cancer cell of (S)-1-
hydroxycyclopent-2-ene-1-carboxamide, comprising an amides and carboxylic acids obtained by hydrolysis
of the nitrile groups of Deidaclin and Tetraphyllin A.
4.1.8.1. Druglikeness of the pharmaceutical form
In Тable 37 are listed values of GPCR ligand, Ion channel modulator, Kinase inhibitor, Nuclear receptor
ligand, Protease inhibitor and Enzyme inhibitor of chemical molecules potentially possible to pass through
the cancer cell membrane and release (S)-1-hydroxycyclopent-2-ene-1-carboxamide.
Tabl. 37. Data for total druglikeness of chemical molecules potentially possible to pass through the cancer
cell membrane and release (S)-1-hydroxycyclopent-2-ene-1-carboxamide
GPCR
ligand
Ion channel
modulator
Kinase
inhibitor
Nuclear receptor
ligand
Protease
inhibitor
Enzyme
inhibitor
Deidaclin amide
0.15
0.09
-0.05
-0.13
0.23
0.53
Deidaclin acid
0.21
0.11
-0.16
0.22
0.14
0.69
Tetraphyllin A amide
0.15
0.09
-0.05
-0.13
0.23
0.53
Tetraphyllin A acid
0.21
0.11
-0.16
0.22
0.14
0.69
Data in Тable 37 show that the amides and carboxylic acids of Deidaclin и Tetraphyllin A have more
pronounced overall drug activity in vivo.
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4.1.8.2. Pharmacological and biological activity of oral active drugs
4.1.8.2.1. Lipinski’s Rule, Ghose Filter and CMC-50-Like Rule
In Table 38 shows the empirical values (without their dimensions) for Lipinski's Rule, Ghose Filter and
CMC-50-Like Rule of chemical molecules potentially possible to pass through the cancer cell membrane and
release (S)-1-hydroxycyclopent-2-ene-1-carboxamide.
Tabl. 38. Lipinski's Rule, Ghose Filter and CMC-50-Like Rule of chemical molecules potentially possible to
pass through the cancer cell membrane and release (S)-1-hydroxycyclopent-2-ene-1-carboxamide
Lipinski's Rule
Ghose Filter
CMC-50-Like Rule
MW
logP
HBA
HBD
MW
logP
AMR
nAtom
MW
logP
AMR
nAtom
Deidaclin amide
289
-2.1
8
5
289
-2.1
63
39
289
-2.1
64
39
Deidaclin acid
290
-1.4
8
5
290
-1.4
67
38
290
-1.4
67
38
Tetraphyllin A amide
290
-2.1
8
5
289
-2.1
64
39
289
-2.1
64
39
Tetraphyllin A acid
290
-1.4
8
5
290
-1.4
64
38
290
-1.4
64
38
They distinguish the three molecular forms (the corresponding amides and carboxylic acids of Deidaclin
and Tetraphyllin A) that meet most requirements. All deviations in individual indicators confirm the
preliminary conditionally accepted approximations in the methodology.
4.1.8.2.2. Veber Filter, MDDR-Like Rule and BBB Likeness
Data on Veber Filter, MDDR-Like Rule and BBB Likeness of chemical molecules potentially possible
to pass through the cancer cell membrane and release (S)-1-hydroxycyclopent-2-ene-1-carboxamide are listed
in Table 39.
Tabl. 39. Data on Veber Filter, MDDR-Like Rule and BBB Likeness of chemical molecules potentially
possible to pass through the cancer cell membrane and release (S)-1-hydroxycyclopent-2-ene-1-
carboxamideса
Veber Filter
MDDR-Like Rule
BBB Likeness
TPSA
nRB
nRB
RC
nRingidB
MW
nAcidGroup
nHB
Deidaclin amide
142
4
4
2
17
289
0
13
Deidaclin acid
137
4
4
2
17
290
1
13
Tetraphyllin A amide
142
4
4
2
17
289
0
13
Tetraphyllin A acid
137
4
4
2
17
290
1
13
There are no significant fluctuations in individual indicators. All "problematic" values correlate with the
pre-entered deviations §3.1.1.2.1.
4.1.8.2.3. QED
The analysis is performed according to §3.1.1.2.3.
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A. uwQED
Data for Unweighted Quantitative Estimate of Druglikeness of the tested compounds are given in Table
40.
Tabl. 40. Unweighted Quantitative Estimate of Druglikeness of chemical molecules potentially possible to
pass through the cancer cell membrane and release (S)-1-hydroxycyclopent-2-ene-1-carboxamide
uwQED
MW
AlogP
HBA
HBD
TPSA
nRB
SAlerts
nAromaRing
uwQED
Deidaclin amide
289
-2.1
8
5
142
4
1
0
0.39
Deidaclin acid
290
-1.8
8
5
137
4
1
0
0.42
Tetraphyllin A amide
289
-2.1
8
5
142
4
1
0
0.39
Tetraphyllin A acid
290
-1.8
8
5
137
4
1
0
0.42
B. wQED
In Table 41 presents the data from the calculations for a Weighted Quantitative Estimate of Druglikeness
of chemical molecules potentially possible to pass through the cancer cell membrane and release (S)-1-
hydroxycyclopent-2-ene-1-carboxamide
Tabl. 41. Weighted Quantitative Estimate of Druglikeness of chemical molecules potentially possible to pass
through the cancer cell membrane and release (S)-1-hydroxycyclopent-2-ene-1-carboxamide
wQED
MW
AlogP
HBA
HBD
TPSA
nRB
Salerts
nAtomRing
wQED
Deidaclin amide
289
-2.1
8
5
142
4
1
0
0.45
Deidaclin acid
290
-1.8
8
5
137
4
1
0
0.48
Tetraphyllin A amide
289
-2.1
8
5
142
4
1
0
0.45
Tetraphyllin A acid
290
-1.8
8
5
137
4
1
0
0.48
uwQED (Tabl.40) and wQED (Tabl.41) of potential pharmaceutical forms including amides and
carboxylic acids obtained by hydrolysis of the nitrile group of Deidaclin and Tetraphyllin A meets the
requirements for conservative treatment.
4.1.8.3. Conclusion from the part
The application of the methodological scheme from §3.1.1.3 for a potential pharmacological form
(§4.1.8), proves maximum qualification for oral medicinal products. No toxicity deviations were observed and
the values were respectively: Oral rat LD50 [mg/kg] for Deidaclin amide и Tetraphyllin A 1448 ≤ 3284 ≤
7449, Deidaclin acid и Tetraphyllin A acid 1132 ≤ 2555 ≤ 5766 и Bioaccumulation factor [conditional units]
Deidaclin amide и Tetraphyllin A 0.00 ≤ 1.5 ≤ 4231, Deidaclin acid и Tetraphyllin A acid 0.02 ≤ 0.16 ≤ 1.5.
This is understandable because both compounds are in isomeric form.
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4.1.9. (1S,4S)-1,4-dihydroxycyclopent-2-ene-1-carboxamide
Subjected to analysis potential pharmaceutical forms for release within the cancer cell of (1S,4S)-1,4-
dihydroxycyclopent-2-ene-1-carboxamide, comprising an amides and carboxylic acids obtained by hydrolysis
of the nitrile groups of Tetraphyllin B, Volkenin and Taraktophyllin.
4.1.9.1. Druglikeness of the pharmaceutical form
In Тable 42 are listed values of GPCR ligand, Ion channel modulator, Kinase inhibitor, Nuclear receptor
ligand, Protease inhibitor and Enzyme inhibitor of chemical molecules potentially possible to pass through
the cancer cell membrane and release (1S,4S)-1,4-dihydroxycyclopent-2-ene-1-carboxamide.
Tabl. 42. Data for total druglikeness of chemical molecules potentially possible to pass through the cancer
cell membrane and release (1S,4S)-1,4-dihydroxycyclopent-2-ene-1-carboxamide
GPCR
ligand
Ion channel
modulator
Kinase
inhibitor
Nuclear receptor
ligand
Protease
inhibitor
Enzyme
inhibitor
Tetraphyllin B amide
0.22
0.15
0.13
0.03
0.28
0.66
Tetraphyllin B acid
0.28
0.17
0.01
0.36
0.19
0.81
Volkenin amide
0.22
0.15
0.13
0.03
0.28
0.66
Volkenin acid
0.28
0.17
0.01
0.36
0.19
0.81
Taraktophyllin amide
0.22
0.15
0.13
0.03
0.28
0.66
Taraktophyllin acid
0.28
0.17
0.01
0.36
0.19
0.81
Data in Тable 42 show that the amides and carboxylic acids of Tetraphyllin B, Volkenin and
Taraktophyllin have more pronounced overall drug activity in vivo.
4.1.9.2. Pharmacological and biological activity of oral active drugs
4.1.9.2.1. Lipinski’s Rule, Ghose Filter and CMC-50-Like Rule
In Table 43 shows the empirical values (without their dimensions) for Lipinski's Rule, Ghose Filter and
CMC-50-Like Rule of chemical molecules potentially possible to pass through the cancer cell membrane and
release (1S,4S)-1,4-dihydroxycyclopent-2-ene-1-carboxamide.
Tabl. 43. Lipinski's Rule, Ghose Filter and CMC-50-Like Rule of chemical molecules potentially possible to
pass through the cancer cell membrane and release (1S,4S)-1,4-dihydroxycyclopent-2-ene-1-carboxamide
Lipinski's Rule
Ghose Filter
CMC-50-Like Rule
MW
logP
HBA
HBD
MW
logP
AMR
nAtom
MW
logP
AMR
nAtom
Tetraphyllin B amide
308
-2.9
9
6
305
-2.9
65
40
305
-2.9
65
40
Tetraphyllin B acid
306
-2.1
9
6
306
-2.1
65
39
306
-2.1
65
39
Volkenin amide
305
-2.9
9
6
305
-2.9
65
40
305
-2.9
65
40
Volkenin acid
306
-2.1
9
6
306
-2.2
65
39
306
-2.1
65
39
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Taraktophyllin amide
305
-2.9
9
6
305
-2.9
65
40
305
-2.9
65
40
Taraktophyllin acid
306
-2.5
9
6
306
-2.1
65
39
306
-2.1
65
39
They distinguish the three molecular forms (the corresponding amides and carboxylic acids of
Tetraphyllin B, Volkenin and Taraktophyllin) that meet most requirements. All deviations in individual
indicators confirm the preliminary conditionally accepted approximations in the methodology.
4.1.9.2.2. Veber Filter, MDDR-Like Rule and BBB Likeness
Data on Veber Filter, MDDR-Like Rule and BBB Likeness of chemical molecules potentially possible
to pass through the cancer cell membrane and release (1S,4S)-1,4-dihydroxycyclopent-2-ene-1-carboxamide
are listed in Table 44.
Tabl. 44. Data on Veber Filter, MDDR-Like Rule and BBB Likeness of chemical molecules potentially
possible to pass through the cancer cell membrane and release (1S,4S)-1,4-dihydroxycyclopent-2-ene-1-
carboxamide
Veber Filter
MDDR-Like Rule
BBB Likeness
TPSA
nRB
nRB
RC
nRingidB
MW
nAcidGroup
nHB
Tetraphyllin B amide
163
4
4
2
18
305
0
15
Tetraphyllin B acid
157
4
4
2
18
306
1
15
Volkenin amide
163
4
4
2
18
305
0
15
Volkenin acid
157
4
4
2
18
306
1
15
Taraktophyllin amide
163
4
4
2
18
305
0
15
Taraktophyllin acid
157
4
4
2
18
306
1
15
There are no significant fluctuations in individual indicators. All "problematic" values correlate with the
pre-entered deviations §3.1.1.2.1.
4.1.9.2.3. QED
The analysis is performed according to §3.1.1.2.3.
A. uwQED
Data for Unweighted Quantitative Estimate of Druglikeness of the tested compounds are given in Table
45.
Tabl. 45. Unweighted Quantitative Estimate of Druglikeness of chemical molecules potentially possible to
pass through the cancer cell membrane and release (1S,4S)-1,4-dihydroxycyclopent-2-ene-1-carboxamide
uwQED
MW
AlogP
HBA
HBD
TPSA
nRB
SAlerts
nAromaRing
uwQED
Tetraphyllin B amide
305
-2.7
9
6
163
4
1
0
0.27
Tetraphyllin B acid
306
-2.5
9
6
157
4
1
0
0.29
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Volkenin amide
305
-2.9
9
6
163
4
1
0
0.27
Volkenin acid
306
-2.5
9
6
157
4
1
0
0.29
Taraktophyllin amide
305
-2.9
9
6
163
4
1
0
0.27
Taraktophyllin acid
306
-2.5
9
6
157
4
1
0
0.29
B. wQED
In Table 46 presents the data from the calculations for a Weighted Quantitative Estimate of Druglikeness
of chemical molecules potentially possible to pass through the cancer cell membrane and release (1S,4S)-1,4-
dihydroxycyclopent-2-ene-1-carboxamide.
Tabl. 46. Weighted Quantitative Estimate of Druglikeness of chemical molecules potentially possible to pass
through the cancer cell membrane and release (1S,4S)-1,4-dihydroxycyclopent-2-ene-1-carboxamide
wQED
MW
AlogP
HBA
HBD
TPSA
nRB
SAlerts
nAtomRing
wQED
Tetraphyllin B amide
305
-2.9
9
6
163
4
1
0
0.35
Tetraphyllin B acid
306
-2.5
9
6
157
4
1
0
0.37
Volkenin amide
305
-2.7
9
6
163
4
1
0
0.35
Volkenin acid
306
-2.5
9
6
157
4
1
0
037
Taraktophyllin amide
305
-2.9
9
6
163
4
1
0
0.35
Taraktophyllin acid
306
-2.5
9
6
157
4
1
0
0.37
uwQED (Table 45) and wQED (Table 46) of potential pharmaceutical forms including amides and
carboxylic acids obtained by hydrolysis of the nitrile group of Tetraphyllin B, Volkenin and Taraktophyllin
meets the requirements for conservative treatment.
4.1.9.3. Conclusion from the part
The application of the methodological scheme from §3.1.1.3 for a potential pharmacological form
(§4.1.9), proves maximum qualification for oral medicinal products. No toxicity deviations were observed and
the values were respectively: Oral rat LD50 [mg/kg] for amide 1606 ≤ 4502 ≤ 12623, acid 1720 ≤ 4318 ≤
10842 и Bioaccumulation factor [conditional units] amide 2.1 ≤ 33 ≤ 533, acid 0.00 ≤ 0.32 ≤ 678. This is
understandable because both compounds are in isomeric form.
4.1.10. (1R,4R)-1,4,5-trihydroxycyclopent-2-ene-1-carboxamide
Subjected to analysis potential pharmaceutical form for release within the cancer cell of (1R,4R)-1,4,5-
trihydroxycyclopent-2-ene-1-carboxamide, comprising an amide and a carboxylic acid obtained by hydrolysis
of the nitrile group of Gynocardin.
4.1.10.1. Druglikeness of the pharmaceutical form
In Тable 47 are listed values of GPCR ligand, Ion channel modulator, Kinase inhibitor, Nuclear receptor
ligand, Protease inhibitor and Enzyme inhibitor of chemical molecules potentially possible to pass through
the cancer cell membrane and release (1R,4R)-1,4,5-trihydroxycyclopent-2-ene-1-carboxamide.
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Tabl. 47. Data for total druglikeness of chemical molecules potentially possible to pass through the cancer
cell membrane and release (1R,4R)-1,4,5-trihydroxycyclopent-2-ene-1-carboxamide
GPCR
ligand
Ion channel
modulator
Kinase
inhibitor
Nuclear receptor
ligand
Protease
inhibitor
Enzyme
inhibitor
Gynocardin amide
0.23
0.14
0.15
0.05
0.29
0.69
Gynocardin acid
0.29
0.15
0.04
0.37
0.21
0.83
Data in Тable 47 show that the amides and carboxylic acids of Gynocardin have more pronounced
overall drug activity in vivo.
4.1.10.2. Pharmacological and biological activity of oral active drugs
4.1.10.2.1. Lipinski’s Rule, Ghose Filter and CMC-50-Like Rule
In Table 48 shows the empirical values (without their dimensions) for Lipinski's Rule, Ghose Filter and
CMC-50-Like Rule of chemical molecules potentially possible to pass through the cancer cell membrane and
release (1R,4R)-1,4,5-trihydroxycyclopent-2-ene-1-carboxamide.
Tabl. 48. Lipinski's Rule, Ghose Filter and CMC-50-Like Rule of chemical molecules potentially possible to
pass through the cancer cell membrane and release (1R,4R)-1,4,5-trihydroxycyclopent-2-ene-1-
carboxamide
Lipinski's Rule
Ghose Filter
CMC-50-Like Rule
MW
logP
HBA
HBD
MW
logP
AMR
nAtom
MW
logP
AMR
nAtom
Gynocardin amide
321
-2.6
10
7
321
-2.6
67
41
321
-2.6
67
41
Gynocardin acid
322
-2.3
10
7
322
-2.3
67
40
322
-2.3
67
40
The two molecular modified forms of Gynocardin meet most requirements. All deviations in individual
indicators confirm the preliminary conditionally accepted approximations in the methodology.
4.1.10.2.2. Veber Filter, MDDR-Like Rule and BBB Likeness
Data on Veber Filter, MDDR-Like Rule and BBB Likeness of chemical molecules potentially possible
to pass through the cancer cell membrane and release (1R,4R)-1,4,5-trihydroxycyclopent-2-ene-1-
carboxamide are listed in Table 49.
Tabl. 49. Data on Veber Filter, MDDR-Like Rule and BBB Likeness of chemical molecules potentially
possible to pass through the cancer cell membrane and release (1R,4R)-1,4,5-trihydroxycyclopent-2-ene-1-
carboxamide
Veber Filter
MDDR-Like Rule
BBB Likeness
TPSA
nRB
nRB
RC
nRingidB
MW
nAcidGroup
nHB
Gynocardin amide
183
4
4
2
19
321
0
17
Gynocardin acid
177
4
4
2
19
322
1
17
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There are no significant fluctuations in individual indicators. All "problematic" values correlate with the
pre-entered deviations §3.1.1.2.1.
4.1.10.2.3. QED
The analysis is performed according to §3.1.1.2.3.
A. uwQED
Data for Unweighted Quantitative Estimate of Druglikeness of the tested compounds are given in Table.
50.
Tabl. 50. Unweighted Quantitative Estimate of Druglikeness of chemical molecules potentially possible to
pass through the cancer cell membrane and release (1R,4R)-1,4,5-trihydroxycyclopent-2-ene-1-
carboxamide
uwQED
MW
AlogP
HBA
HBD
TPSA
nRB
sAlerts
nAromaRing
uwQED
Gynocardin amide
321
-3.7
10
7
183
4
1
0
0.19
Gynocardin acid
322
-3.3
10
7
177
4
1
0
0.21
B. wQED
In Table 51 presents the data from the calculations for a Weighted Quantitative Estimate of Druglikeness
of chemical molecules potentially possible to pass through the cancer cell membrane and release (1R,4R)-
1,4,5-trihydroxycyclopent-2-ene-1-carboxamide.
Tabl. 51. Weighted Quantitative Estimate of Druglikeness of chemical molecules potentially possible to pass
through the cancer cell membrane and release (1R,4R)-1,4,5-trihydroxycyclopent-2-ene-1-carboxamide
wQED
MW
AlogP
HBA
HBD
TPSA
nRB
SAlerts
nAtomRing
wQED
Gynocardin amide
321
-3.7
10
7
183
4
1
0
0.28
Gynocardin acid
322
-3.3
10
7
177
4
1
0
0.29
uwQED (Table 50) and wQED (Table 51) of a potential pharmaceutical form including amide and
carboxylic acid obtained by hydrolysis of the nitrile group of Gynocardin meets the requirements for
conservative treatment.
4.1.10.3. Conclusion from the part
The application of the methodological scheme from §3.1.1.3 for a potential pharmacological form
(§4.1.10), proves maximum qualification for oral medicinal products. No toxicity deviations were observed
and the values were respectively: Oral rat LD50 [mg/kg] for amide 2957 ≤ 8312 ≤ 23360, acid 3059 ≤ 7704 ≤
19402 и Bioaccumulation factor [conditional units] amide 2.5 ≤ 39 ≤ 638, acid 0.00 ≤ 0.31 ≤ 707.
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4.1.11. (Z)-2-((4S,6R)-4,6-dihydroxycyclohex-2-en-1-ylidene)acetamide
Subjected to analysis potential pharmaceutical form for release within the cancer cell of (Z)-2-((4S,6R)-
4,6-dihydroxycyclohex-2-en-1-ylidene)acetamide, comprising an amide and a carboxylic acid obtained by
hydrolysis of the nitrile group of Menisdaurin.
4.1.11.1. Druglikeness of the pharmaceutical form
In Тable 52 are listed values of GPCR ligand, Ion channel modulator, Kinase inhibitor, Nuclear receptor
ligand, Protease inhibitor and Enzyme inhibitor of chemical molecules potentially possible to pass through
the cancer cell membrane and release (Z)-2-((4S,6R)-4,6-dihydroxycyclohex-2-en-1-ylidene)acetamide.
Tabl. 52. Data for total druglikeness of chemical molecules potentially possible to pass through the cancer
cell membrane and release (Z)-2-((4S,6R)-4,6-dihydroxycyclohex-2-en-1-ylidene)acetamide
GPCR
ligand
Ion channel
modulator
Kinase
inhibitor
Nuclear receptor
ligand
Protease
inhibitor
Enzyme
inhibitor
Menisdaurin amide
0.53
0.35
0.22
0.42
0.27
0.99
Menisdaurin acid
0.57
0.47
0.21
0.68
0.34
1.01
Data in Тable 52 show that the amides and carboxylic acids of Menisdaurin have more pronounced
overall drug activity in vivo.
4.1.11.2. Pharmacological and biological activity of oral active drugs
4.1.11.2.1. Lipinski’s Rule, Ghose Filter and CMC-50-Like Rule
In Table 53 shows the empirical values (without their dimensions) for Lipinski's Rule, Ghose Filter and
CMC-50-Like Rule of chemical molecules potentially possible to pass through the cancer cell membrane and
release (Z)-2-((4S,6R)-4,6-dihydroxycyclohex-2-en-1-ylidene)acetamide.
Tabl. 53. Lipinski's Rule, Ghose Filter and CMC-50-Like Rule of chemical molecules potentially possible to
pass through the cancer cell membrane and release (Z)-2-((4S,6R)-4,6-dihydroxycyclohex-2-en-1-
ylidene)acetamide
Lipinski's Rule
Ghose Filter
CMC-50-Like Rule
MW
logP
HBA
HBD
MW
logP
AMR
nAtom
MW
logP
AMR
nAtom
Menisdaurin amide
331
-2.7
9
6
331
-2.6
74
44
331
-2.6
74
44
Menisdaurin acid
332
-1.9
9
6
332
-1.9
74
43
332
-1.9
74
43
The two molecular modified forms of Menisdaurin meet most requirements. All deviations in individual
indicators confirm the preliminary conditionally accepted approximations in the methodology.
4.1.11.2.2. Veber Filter, MDDR-Like Rule and BBB Likeness
Data on Veber Filter, MDDR-Like Rule and BBB Likeness of chemical molecules potentially possible
to pass through the cancer cell membrane and release (Z)-2-((4S,6R)-4,6-dihydroxycyclohex-2-en-1-
ylidene)acetamide are listed in Table 54.
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Tabl. 54. Data on Veber Filter, MDDR-Like Rule and BBB Likeness of chemical molecules potentially
possible to pass through the cancer cell membrane and release (Z)-2-((4S,6R)-4,6-dihydroxycyclohex-2-en-
1-ylidene)acetamide
Veber Filter
MDDR-Like Rule
BBB Likeness
TPSA
nRB
nRB
RC
nRingidB
MW
nAcidGroup
nHB
Menisdaurin amide
163
4
4
2
20
331
0
15
Menisdaurin acid
157
4
4
2
20
332
1
15
There are no significant fluctuations in individual indicators. All "problematic" values correlate with the
pre-entered deviations §3.1.1.2.1.
4.1.11.2.3. QED
The analysis is performed according to §3.1.1.2.3.
A. uwQED
Data for Unweighted Quantitative Estimate of Druglikeness of the tested compounds are given in Table
55.
Tabl. 55. Unweighted Quantitative Estimate of Druglikeness of chemical molecules potentially possible to
pass through the cancer cell membrane and release (Z)-2-((4S,6R)-4,6-dihydroxycyclohex-2-en-1-
ylidene)acetamide
uwQED
MW
AlogP
HBA
HBD
TPSA
nRB
sAlerts
nAromaRing
uwQED
Menisdaurin amide
331
-3.1
9
6
163
4
1
0
0.26
Menisdaurin acid
332
-2.7
9
6
157
4
1
0
0.29
B. wQED
In Table 56 presents the data from the calculations for a Weighted Quantitative Estimate of Druglikeness
of chemical molecules potentially possible to pass through the cancer cell membrane and release (Z)-2-
((4S,6R)-4,6-dihydroxycyclohex-2-en-1-ylidene)acetamide.
Tabl. 56. Weighted Quantitative Estimate of Druglikeness of chemical molecules potentially possible to pass
through the cancer cell membrane and release (Z)-2-((4S,6R)-4,6-dihydroxycyclohex-2-en-1-
ylidene)acetamide
wQED
MW
AlogP
HBA
HBD
TPSA
nRB
SAlerts
nAtomRing
wQED
Menisdaurin amide
331
-3.1
9
6
163
4
1
0
0.34
Menisdaurin acid
332
-2.7
9
6
157
4
1
0
0.36
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uwQED (Table 55) and wQED (Table 56) of a potential pharmaceutical form including amide and
carboxylic acid obtained by hydrolysis of the nitrile group of Menisdaurin meets the requirements for
conservative treatment.
4.1.11.3. Conclusion from the part
The application of the methodological scheme from §3.1.1.3 for a potential pharmacological form
(§4.1.11), proves maximum qualification for oral medicinal products. No toxicity deviations were observed
and the values were respectively: Oral rat LD50 [mg/kg] for amide 3924 ≤ 10845 ≤ 29968, acid 2977 ≤ 7383
≤ 18307 и Bioaccumulation factor [conditional units] amide 0.85 ≤ 14 ≤ 224, acid 0.00 ≤ 0.30 ≤ 617.
4.1.12. (R)-2-hydroxy-3-methylbutanamide
Subjected to analysis potential pharmaceutical form for release within the cancer cell of (R)-2-hydroxy-
3-methylbutanamide, comprising an amide and a carboxylic acid obtained by hydrolysis of the nitrile group
of Epiheterodendrin.
4.1.12.1. Druglikeness of the pharmaceutical form
In Тable 57 are listed values of GPCR ligand, Ion channel modulator, Kinase inhibitor, Nuclear receptor
ligand, Protease inhibitor and Enzyme inhibitor of chemical molecules potentially possible to pass through
the cancer cell membrane and release (R)-2-hydroxy-3-methylbutanamide.
Tabl. 57. Data for total druglikeness of chemical molecules potentially possible to pass through the cancer
cell membrane and release (R)-2-hydroxy-3-methylbutanamide
GPCR
ligand
Ion channel
modulator
Kinase
inhibitor
Nuclear receptor
ligand
Protease
inhibitor
Enzyme
inhibitor
Epiheterodendrin amide
0.02
-0.08
-0.26
-0.44
0.15
0.31
Epiheterodendrin acid
0.17
0.17
-0.25
0.16
0.21
0.52
Data in Тable 57 show that the amides and carboxylic acids of Epiheterodendrin have more pronounced
overall drug activity in vivo.
4.1.12.2. Pharmacological and biological activity of oral active drugs
4.1.12.2.1. Lipinski’s Rule, Ghose Filter and CMC-50-Like Rule
In Table 58 shows the empirical values (without their dimensions) for Lipinski's Rule, Ghose Filter
and CMC-50-Like Rule of chemical molecules potentially possible to pass through the cancer cell
membrane and release (R)-2-hydroxy-3-methylbutanamide.
Tabl. 58. Lipinski's Rule, Ghose Filter and CMC-50-Like Rule of chemical molecules potentially possible to
pass through the cancer cell membrane and release (R)-2-hydroxy-3-methylbutanamide
Lipinski's Rule
Ghose Filter
CMC-50-Like Rule
MW
logP
HBA
HBD
MW
logP
AMR
nAtom
MW
logP
AMR
nAtom
Epiheterodendrin amide
279
-1.8
8
5
279
-1.8
60
40
279
-1.8
60
40
Epiheterodendrin acid
280
-1.0
8
5
280
-1.0
60
39
280
-1.0
60
39
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The two molecular modified forms of Epiheterodendrin meet most requirements. All deviations in
individual indicators confirm the preliminary conditionally accepted approximations in the methodology.
4.1.12.2.2. Veber Filter, MDDR-Like Rule and BBB Likeness
Data on Veber Filter, MDDR-Like Rule and BBB Likeness of chemical molecules potentially possible
to pass through the cancer cell membrane and release (R)-2-hydroxy-3-methylbutanamide are listed in Table
59.
Table. 59. Data on Veber Filter, MDDR-Like Rule and BBB Likeness of chemical molecules potentially
possible to pass through the cancer cell membrane and release (R)-2-hydroxy-3-methylbutanamide
Veber Filter
MDDR-Like Rule
BBB Likeness
TPSA
nRB
nRB
RC
nRingidB
MW
nAcidGroup
nHB
Epiheterodendrin amide
142
5
5
1
14
279
0
13
Epiheterodendrin acid
137
5
5
1
14
280
1
13
There are no significant fluctuations in individual indicators. All "problematic" values correlate with the
pre-entered deviations §3.1.1.2.1.
4.1.12.2.3. QED
The analysis is performed according to §3.1.1.2.3.
A. uwQED
Data for Unweighted Quantitative Estimate of Druglikeness of the tested compounds are given in Table
60.
Tabl. 60. Unweighted Quantitative Estimate of Druglikeness of chemical molecules potentially possible to
pass through the cancer cell membrane and release (R)-2-hydroxy-3-methylbutanamide
uwQED
MW
AlogP
HBA
HBD
TPSA
nRB
sAlerts
nAromaRing
uwQED
Epiheterodendrin amide
279
-2.4
8
5
142
5
0
0
0.37
Epiheterodendrin acid
280
-2.0
8
5
137
5
0
0
0.40
B. wQED
In Table 61 presents the data from the calculations for a Weighted Quantitative Estimate of Druglikeness
of chemical molecules potentially possible to pass through the cancer cell membrane and release (R)-2-
hydroxy-3-methylbutanamide
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Tabl. 61. Weighted Quantitative Estimate of Druglikeness of chemical molecules potentially possible to pass
through the cancer cell membrane and release (R)-2-hydroxy-3-methylbutanamide
wQED
MW
AlogP
HBA
HBD
TPSA
nRB
SAlerts
nAtomRing
wQED
Epiheterodendrin amide
279
-2.4
8
5
142
5
0
0
0.43
Epiheterodendrin acid
280
-2.0
8
5
137
5
0
0
0.46
uwQED (Тable 60) and wQED (Тable 61) of a potential pharmaceutical form including amide and
carboxylic acid obtained by hydrolysis of the nitrile group of Epiheterodendrin meets the requirements for
conservative treatment.
4.1.12.3. Conclusion from the part
The application of the methodological scheme from §3.1.1.3 for a potential pharmacological form
(§4.1.12), proves maximum qualification for oral medicinal products. No toxicity deviations were observed
and the values were respectively: Oral rat LD50 [mg/kg] for amide 2991 ≤ 8380 ≤ 23479, acid 5167 ≤ 13131
≤ 33365 и Bioaccumulation factor [ conditional units ] amide 5.5 ≤ 89 ≤ 1448, acid 0.03 ≤ 0.61 ≤ 14.
4.1.13. (E)-2-((4S,5R,6R)-4,5,6-trihydroxycyclohex-2-en-1-ylidene)acetamide
Subjected to analysis potential pharmaceutical form for release within the cancer cell of (E)-2-
((4S,5R,6R)-4,5,6-trihydroxycyclohex-2-en-1-ylidene)acetamide, comprising an amide and a carboxylic acid
obtained by hydrolysis of the nitrile group of Griffonin.
4.1.13.1. Druglikeness of the pharmaceutical form
In Тable 62 are listed values of GPCR ligand, Ion channel modulator, Kinase inhibitor, Nuclear receptor
ligand, Protease inhibitor and Enzyme inhibitor of chemical molecules potentially possible to pass through
the cancer cell membrane and release (E)-2-((4S,5R,6R)-4,5,6-trihydroxycyclohex-2-en-1-ylidene)acetamide.
Tabl. 62. Data for total druglikeness of chemical molecules potentially possible to pass through the cancer
cell membrane and release (E)-2-((4S,5R,6R)-4,5,6-trihydroxycyclohex-2-en-1-ylidene)acetamide
GPCR
ligand
Ion channel
modulator
Kinase
inhibitor
Nuclear receptor
ligand
Protease
inhibitor
Enzyme
inhibitor
Griffonin amide
0.42
0.13
0.13
0.30
0.10
0.39
Griffonin acid
0.47
0.24
0.12
0.55
0.17
0.70
Data in Тable 62 show that the amides and carboxylic acids of Griffonin have pronounced overall drug
activity in vivo.
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4.1.13.2. Pharmacological and biological activity of oral active drugs
4.1.13.2.1. Lipinski’s Rule, Ghose Filter and CMC-50-Like Rule
In Table 63 shows the empirical values (without their dimensions) for Lipinski's Rule, Ghose Filter and
CMC-50-Like Rule of chemical molecules potentially possible to pass through the cancer cell membrane and
release (E)-2-((4S,5R,6R)-4,5,6-trihydroxycyclohex-2-en-1-ylidene)acetamide.
Tabl. 63. Lipinski's Rule, Ghose Filter and CMC-50-Like Rule of chemical molecules potentially possible to
pass through the cancer cell membrane and release (E)-2-((4S,5R,6R)-4,5,6-trihydroxycyclohex-2-en-1-
ylidene)acetamide
Lipinski's Rule
Ghose Filter
CMC-50-Like Rule
MW
logP
HBA
HBD
MW
logP
AMR
nAtom
MW
logP
AMR
nAtom
Griffonin amide
347
-3.2
10
7
347
-3.2
77
45
347
-3.2
77
45
Griffonin acid
348
-2.5
10
7
348
-2.5
77
44
348
-2.5
77
44
The two molecular modified forms of Griffonin meet most requirements. All deviations in individual
indicators confirm the preliminary conditionally accepted approximations in the methodology.
4.1.13.2.2. Veber Filter, MDDR-Like Rule and BBB Likeness
Data on Veber Filter, MDDR-Like Rule and BBB Likeness of chemical molecules potentially possible
to pass through the cancer cell membrane and release (E)-2-((4S,5R,6R)-4,5,6-trihydroxycyclohex-2-en-1-
ylidene)acetamide are listed in Table 64.
Tabl. 64. Data on Veber Filter, MDDR-Like Rule and BBB Likeness of chemical molecules potentially
possible to pass through the cancer cell membrane and release (E)-2-((4S,5R,6R)-4,5,6-trihydroxycyclohex-
2-en-1-ylidene)acetamide
Veber Filter
MDDR-Like Rule
BBB Likeness
TPSA
nRB
nRB
RC
nRingidB
MW
nAcidGroup
nHB
Griffonin amide
183
4
4
2
21
347
0
17
Griffonin acid
177
4
4
2
21
348
1
17
There are no significant fluctuations in individual indicators. All "problematic" values correlate with the
pre-entered deviations §3.1.1.2.1.
4.1.13.2.3. QED
The analysis is performed according to §3.1.1.2.3.
A. uwQED
Data for Unweighted Quantitative Estimate of Druglikeness of the tested compounds are given in Table
65.
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Tabl. 65. Unweighted Quantitative Estimate of Druglikeness of chemical molecules potentially possible to
pass through the cancer cell membrane and release (E)-2-((4S,5R,6R)-4,5,6-trihydroxycyclohex-2-en-1-
ylidene)acetamide
uwQED
MW
AlogP
HBA
HBD
TPSA
nRB
sAlerts
nAromaRing
uwQED
Griffonin amide
347
-3.3
10
7
183
4
1
0
0.20
Griffonin acid
348
-2.9
10
7
177
4
1
0
0.22
B. wQED
In Table 66 presents the data from the calculations for a Weighted Quantitative Estimate of Druglikeness
of chemical molecules potentially possible to pass through the cancer cell membrane and release (E)-2-
((4S,5R,6R)-4,5,6-trihydroxycyclohex-2-en-1-ylidene)acetamide.
Tabl. 66. Weighted Quantitative Estimate of Druglikeness of chemical molecules potentially possible to pass
through the cancer cell membrane and release (E)-2-((4S,5R,6R)-4,5,6-trihydroxycyclohex-2-en-1-
ylidene)acetamide
wQED
MW
AlogP
HBA
HBD
TPSA
nRB
SAlerts
nAtomRing
wQED
Griffonin amide
347
-3.3
10
7
183
4
1
0
0.29
Griffonin acid
348
-2.9
10
7
177
4
1
0
0.31
uwQED (Table 65) and wQED (Table 66) of a potential pharmaceutical form including amide and
carboxylic acid obtained by hydrolysis of the nitrile group of Griffonin meets the requirements for
conservative treatment.
4.1.13.3. Conclusion from the part
The application of the methodological scheme from §3.1.1.3 for a potential pharmacological form
(§4.1.13), proves maximum qualification for oral medicinal products. No toxicity deviations were observed
and the values were respectively: Oral rat LD50 [mg/kg] for amide 5016 ≤ 13956 ≤ 38832, acid 4015 ≤ 10006
≤ 24938 и Bioaccumulation factor [conditional units] amide 0.86 ≤ 14 ≤ 228, acid 0.00 ≤ 0.25 ≤ 567.
4.1.14. (Z)-2-((4R,5R,6S)-5,6-dihydroxy-4-methoxycyclohex-2-en-1-ylidene)acetamide
Subjected to analysis potential pharmaceutical form for release within the cancer cell of (Z)-2-
((4R,5R,6S)-5,6-dihydroxy-4-methoxycyclohex-2-en-1-ylidene)acetamide, comprising an amide and a
carboxylic acid obtained by hydrolysis of the nitrile group of Bauhinin.
4.1.14.1. Druglikeness of the pharmaceutical form
In Тable 67 are listed values of GPCR ligand, Ion channel modulator, Kinase inhibitor, Nuclear receptor
ligand, Protease inhibitor and Enzyme inhibitor of chemical molecules potentially possible to pass through
the cancer cell membrane and release (Z)-2-((4R,5R,6S)-5,6-dihydroxy-4-methoxycyclohex-2-en-1-
ylidene)acetamide.
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Tabl. 67. Data for total druglikeness of chemical molecules potentially possible to pass through the cancer
cell membrane and release (Z)-2-((4R,5R,6S)-5,6-dihydroxy-4-methoxycyclohex-2-en-1-ylidene)acetamide
GPCR
ligand
Ion channel
modulator
Kinase
inhibitor
Nuclear receptor
ligand
Protease
inhibitor
Enzyme
inhibitor
Bauhinin amide
0.42
0.18
0.19
0.30
0.13
0.64
Bauhinin acid
0.46
0.29
0.18
0.54
0.19
0.65
Data in Тable 67 show that the amides and carboxylic acids of Bauhinin have pronounced overall drug
activity in vivo.
4.1.14.2. Pharmacological and biological activity of oral active drugs
4.1.14.2.1. Lipinski’s Rule, Ghose Filter and CMC-50-Like Rule
In Table 68 shows the empirical values (without their dimensions) for Lipinski's Rule, Ghose Filter and
CMC-50-Like Rule of chemical molecules potentially possible to pass through the cancer cell membrane and
release (Z)-2-((4R,5R,6S)-5,6-dihydroxy-4-methoxycyclohex-2-en-1-ylidene)acetamide.
Tabl. 68. Lipinski's Rule, Ghose Filter and CMC-50-Like Rule of chemical molecules potentially possible to
pass through the cancer cell membrane and release (Z)-2-((4R,5R,6S)-5,6-dihydroxy-4-methoxycyclohex-2-
en-1-ylidene)acetamide
Lipinski's Rule
Ghose Filter
CMC-50-Like Rule
MW
logP
HBA
HBD
MW
logP
AMR
nAtom
MW
logP
AMR
nAtom
Bauhinin amide
361
-3.1
10
6
362
-3.1
82
48
361
-3.1
82
48
Bauhinin acid
362
-2.4
10
6
362
-2.4
82
47
362
-2.4
82
47
The two molecular modified forms of Bauhinin meet most requirements. All deviations in individual
indicators confirm the preliminary conditionally accepted approximations in the methodology.
4.1.14.2.2. Veber Filter, MDDR-Like Rule and BBB Likeness
Data on Veber Filter, MDDR-Like Rule and BBB Likeness of chemical molecules potentially possible
to pass through the cancer cell membrane and release (Z)-2-((4R,5R,6S)-5,6-dihydroxy-4-methoxycyclohex-2-
en-1-ylidene)acetamide are listed in Table 69.
Tabl. 69. Data on Veber Filter, MDDR-Like Rule and BBB Likeness of chemical molecules potentially
possible to pass through the cancer cell membrane and release (Z)-2-((4R,5R,6S)-5,6-dihydroxy-4-
methoxycyclohex-2-en-1-ylidene)acetamide
Veber Filter
MDDR-Like Rule
BBB Likeness
TPSA
nRB
nRB
RC
nRingidB
MW
nAcidGroup
nHB
Bauhinin amide
172
5
5
2
21
361
0
16
Bauhinin acid
166
5
5
2
21
362
1
16
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There are no significant fluctuations in individual indicators. All "problematic" values correlate with the
pre-entered deviations §3.1.1.2.1.
4.1.14.2.3. QED
The analysis is performed according to §3.1.1.2.3.
C. uwQED
Data for Unweighted Quantitative Estimate of Druglikeness of the tested compounds are given in Table
70.
Tabl. 70. Unweighted Quantitative Estimate of Druglikeness of chemical molecules potentially possible to
pass through the cancer cell membrane and release (Z)-2-((4R,5R,6S)-5,6-dihydroxy-4-methoxycyclohex-2-
en-1-ylidene)acetamide
uwQED
MW
AlogP
HBA
HBD
TPSA
nRB
sAlerts
nAromaRing
uwQED
Bauhinin amide
361
-2.9
10
6
172
5
1
0
0.24
Bauhinin acid
362
-2.5
10
6
166
5
1
0
0.26
D. wQED
Table 71 presents the data from the calculations for a Weighted Quantitative Estimate of Druglikeness
of chemical molecules potentially possible to pass through the cancer cell membrane and release (Z)-2-
((4R,5R,6S)-5,6-dihydroxy-4-methoxycyclohex-2-en-1-ylidene)acetamide.
Tabl. 71. Weighted Quantitative Estimate of Druglikeness of chemical molecules potentially possible to pass
through the cancer cell membrane and release (Z)-2-((4R,5R,6S)-5,6-dihydroxy-4-methoxycyclohex-2-en-1-
ylidene)acetamide
wQED
MW
AlogP
HBA
HBD
TPSA
nRB
SAlerts
nAtomRing
wQED
Bauhinin amide
361
-2.9
10
6
172
5
1
0
0.33
Bauhinin acid
362
-2.5
10
6
166
5
1
0
0.36
uwQED (Table 70) and wQED (Table 71) of a potential pharmaceutical form including amide and
carboxylic acid obtained by hydrolysis of the nitrile group of Lithospermoside meets the requirements for
conservative treatment.
4.1.14.3. Conclusion from the part
The application of the methodological scheme from §3.1.1.3 for a potential pharmacological form
(§4.1.14), proves maximum qualification for oral medicinal products. No toxicity deviations were observed
and the values were respectively: Oral rat LD50 [ mg/kg ] for amide 3765 ≤ 10452 ≤ 29017, acid 3521 ≤ 9817
≤ 27375 and Bioaccumulation factor [ conditional units ] amide 0.96 ≤ 16 ≤ 255, acid 0,00 ≤ 0.28 ≤ 560.
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4.1.15. (E)-2-((4R,6S)-4,6-dihydroxycyclohex-2-en-1-ylidene)acetamide
Subjected to analysis potential pharmaceutical form for release within the cancer cell of (E)-2-((4R,6S)-
4,6-dihydroxycyclohex-2-en-1-ylidene)acetamide, comprising an amide and a carboxylic acid obtained by
hydrolysis of the nitrile group of Purshianin.
4.1.15.1. Druglikeness of the pharmaceutical form
In Тable 72 are listed values of GPCR ligand, Ion channel modulator, Kinase inhibitor, Nuclear receptor
ligand, Protease inhibitor and Enzyme inhibitor of chemical molecules potentially possible to pass through
the cancer cell membrane and release (E)-2-((4R,6S)-4,6-dihydroxycyclohex-2-en-1-ylidene)acetamide.
Tabl. 72. Data for total druglikeness of chemical molecules potentially possible to pass through the cancer
cell membrane and release (E)-2-((4R,6S)-4,6-dihydroxycyclohex-2-en-1-ylidene)acetamide
GPCR
ligand
Ion channel
modulator
Kinase
inhibitor
Nuclear receptor
ligand
Protease
inhibitor
Enzyme
inhibitor
Purshianin amide
0.53
0.35
0.22
0.42
0.27
0.99
Purshianin acid
0.57
0.47
0.21
0.68
0.34
1.01
Data in Тable 72 show that the amides and carboxylic acids of Purshianin have pronounced overall drug
activity in vivo.
4.1.15.2. Pharmacological and biological activity of oral active drugs
4.1.15.2.1. Lipinski’s Rule, Ghose Filter and CMC-50-Like Rule
In Table 73 shows the empirical values (without their dimensions) for Lipinski's Rule, Ghose Filter and
CMC-50-Like Rule of chemical molecules potentially possible to pass through the cancer cell membrane and
release (E)-2-((4R,6S)-4,6-dihydroxycyclohex-2-en-1-ylidene)acetamide.
Tabl. 73. Lipinski's Rule, Ghose Filter and CMC-50-Like Rule of chemical molecules potentially possible to
pass through the cancer cell membrane and release (R)-(E)-2-((4R,6S)-4,6-dihydroxycyclohex-2-en-1-
ylidene)acetamide
Lipinski's Rule
Ghose Filter
CMC-50-Like Rule
MW
logP
HBA
HBD
MW
logP
AMR
nAtom
MW
logP
AMR
nAtom
Purshianin amide
331
-2.6
9
6
331
-2.6
74
44
331
-2.6
74
44
Purshianin acid
332
-1.9
9
6
332
-1.9
74
43
332
-1.9
74
43
The two molecular modified forms of Purshianin meet most requirements. All deviations in individual
indicators confirm the preliminary conditionally accepted approximations in the methodology.
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4.1.15.2.2. Veber Filter, MDDR-Like Rule and BBB Likeness
Data on Veber Filter, MDDR-Like Rule and BBB Likeness of chemical molecules potentially possible
to pass through the cancer cell membrane and release (E)-2-((4R,6S)-4,6-dihydroxycyclohex-2-en-1-
ylidene)acetamide are listed in Table 74.
Tabl. 74. Data on Veber Filter, MDDR-Like Rule and BBB Likeness of chemical molecules potentially
possible to pass through the cancer cell membrane and release (E)-2-((4R,6S)-4,6-dihydroxycyclohex-2-en-
1-ylidene)acetamide
Veber Filter
MDDR-Like Rule
BBB Likeness
TPSA
nRB
nRB
RC
nRingidB
MW
nAcidGroup
nHB
Purshianin amide
163
4
4
2
20
331
0
15
Purshianin acid
157
4
4
2
20
332
1
15
There are no significant fluctuations in individual indicators. All "problematic" values correlate with the
pre-entered deviations §3.1.1.2.1.
4.1.15.2.3. QED
The analysis is performed according to §3.1.1.2.3.
A. uwQED
Data for Unweighted Quantitative Estimate of Druglikeness of the tested compounds are given in Table
75.
Tabl. 75. Unweighted Quantitative Estimate of Druglikeness of chemical molecules potentially possible to
pass through the cancer cell membrane and release (E)-2-((4R,6S)-4,6-dihydroxycyclohex-2-en-1-
ylidene)acetamide
uwQED
MW
AlogP
HBA
HBD
TPSA
nRB
sAlerts
nAromaRing
uwQED
Purshianin amide
331
-3.1
9
6
163
4
1
0
0.27
Purshianin acid
332
-2.7
9
6
157
4
1
0
0.29
B. wQED
Table 76 presents the data from the calculations for a Weighted Quantitative Estimate of Druglikeness
of chemical molecules potentially possible to pass through the cancer cell membrane and release (E)-2-
((4R,6S)-4,6-dihydroxycyclohex-2-en-1-ylidene)acetamide.
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Tabl. 76. Weighted Quantitative Estimate of Druglikeness of chemical molecules potentially possible to pass
through the cancer cell membrane and release (E)-2-((4R,6S)-4,6-dihydroxycyclohex-2-en-1-
ylidene)acetamide
wQED
MW
AlogP
HBA
HBD
TPSA
nRB
SAlerts
nAtomRing
wQED
Purshianin amide
331
-3.1
9
6
163
4
1
0
0.34
Purshianin acid
322
-2.7
9
6
157
4
1
0
0.36
uwQED (Table 75) and wQED (Table 76) of a potential pharmaceutical form including amide and
carboxylic acid obtained by hydrolysis of the nitrile group of Lithospermoside meets the requirements for
conservative treatment.
4.1.15.3. Conclusion from the part
The application of the methodological scheme from §3.1.1.3 for a potential pharmacological form
(§4.1.15), proves maximum qualification 3924 ≤ 10845 ≤ 29968, acid 2977 ≤ 7383 ≤ 18307 and
Bioaccumulation factor [conditional units] amide 0.85 ≤ 14 ≤ 224, acid 0.00 ≤ 0.30 ≤ 617.
4.1.16. (E)-2-((4S,5R,6R)-4,5,6-trihydroxycyclohex-2-en-1-ylidene)acetamide
Subjected to analysis potential pharmaceutical form for release within the cancer cell of (R)-2-hydroxy-
2-phenylacetamide, comprising an amide and a carboxylic acid obtained by hydrolysis of the nitrile group of
Lithospermoside.
4.1.16.1. Druglikeness of the pharmaceutical form
In Тable 77 are listed values of GPCR ligand, Ion channel modulator, Kinase inhibitor, Nuclear receptor
ligand, Protease inhibitor and Enzyme inhibitor of chemical molecules potentially possible to pass through
the cancer cell membrane and release (E)-2-((4S,5R,6R)-4,5,6-trihydroxycyclohex-2-en-1-ylidene)acetamide.
Tabl. 77. Data for total druglikeness of chemical molecules potentially possible to pass through the cancer
cell membrane and release (E)-2-((4S,5R,6R)-4,5,6-trihydroxycyclohex-2-en-1-ylidene)acetamide
GPCR
ligand
Ion channel
modulator
Kinase
inhibitor
Nuclear receptor
ligand
Protease
inhibitor
Enzyme
inhibitor
Lithospermoside amide
0.43
0.13
0.13
0.30
0.10
0.69
Lithospermoside acid
0.47
0.24
0.12
0.55
0.17
0.70
Data in Тable 77 show that the amides and carboxylic acids of Lithospermoside have pronounced overall
drug activity in vivo.
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4.1.16.2. Pharmacological and biological activity of oral active drugs
4.1.16.2.1. Lipinski’s Rule, Ghose Filter and CMC-50-Like Rule
In Table 78 shows the empirical values (without their dimensions) for Lipinski's Rule, Ghose Filter and
CMC-50-Like Rule of chemical molecules potentially possible to pass through the cancer cell membrane and
release (E)-2-((4S,5R,6R)-4,5,6-trihydroxycyclohex-2-en-1-ylidene)acetamide.
Tabl. 78. Lipinski's Rule, Ghose Filter and CMC-50-Like Rule of chemical molecules potentially possible to
pass through the cancer cell membrane and release (E)-2-((4S,5R,6R)-4,5,6-trihydroxycyclohex-2-en-1-
ylidene)acetamide
Lipinski's Rule
Ghose Filter
CMC-50-Like Rule
MW
logP
HBA
HBD
MW
logP
AMR
nAtom
MW
logP
AMR
nAtom
Lithospermoside amide
347
-3.2
10
7
347
-3.2
77
45
347
-3.2
77
45
Lithospermoside acid
348
-2.5
10
7
348
-2.5
77
44
348
-2.5
77
44
The two molecular modified forms of Lithospermoside meet most requirements. All deviations in
individual indicators confirm the preliminary conditionally accepted approximations in the methodology.
4.1.16.2.2. Veber Filter, MDDR-Like Rule and BBB Likeness
Data on Veber Filter, MDDR-Like Rule and BBB Likeness of chemical molecules potentially possible
to pass through the cancer cell membrane and release (E)-2-((4S,5R,6R)-4,5,6-trihydroxycyclohex-2-en-1-
ylidene)acetamide are listed in Table 79.
Tabl. 79. Data on Veber Filter, MDDR-Like Rule and BBB Likeness of chemical molecules potentially
possible to pass through the cancer cell membrane and release (E)-2-((4S,5R,6R)-4,5,6-trihydroxycyclohex-
2-en-1-ylidene)acetamide
Veber Filter
MDDR-Like Rule
BBB Likeness
TPSA
nRB
nRB
RC
nRingidB
MW
nAcidGroup
nHB
Lithospermoside amide
183
4
4
2
21
347
0
17
Lithospermoside acid
177
4
4
2
21
348
1
17
There are no significant fluctuations in individual indicators. All "problematic" values correlate with the
pre-entered deviations §3.1.1.2.1.
4.1.16.2.3. QED
The analysis is performed according to §3.1.1.2.3.
A. uwQED
Data for Unweighted Quantitative Estimate of Druglikeness of the tested compounds are given in Tabl.
80.
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Tabl. 80. Unweighted Quantitative Estimate of Druglikeness of chemical molecules potentially possible to
pass through the cancer cell membrane and release (E)-2-((4S,5R,6R)-4,5,6-trihydroxycyclohex-2-en-1-
ylidene)acetamide
uwQED
MW
AlogP
HBA
HBD
TPSA
nRB
sAlerts
nAromaRing
uwQED
Lithospermoside amide
347
-3.3
10
7
183
4
1
0
0.204
Lithospermoside acid
348
-2.9
10
7
177
4
1
0
0.222
B. wQED
Table 81 presents the data from the calculations for a Weighted Quantitative Estimate of Druglikeness
of chemical molecules potentially possible to pass through the cancer cell membrane and release (E)-2-
((4S,5R,6R)-4,5,6-trihydroxycyclohex-2-en-1-ylidene)acetamide.
Tabl. 81. Weighted Quantitative Estimate of Druglikeness of chemical molecules potentially possible to pass
through the cancer cell membrane and release (E)-2-((4S,5R,6R)-4,5,6-trihydroxycyclohex-2-en-1-
ylidene)acetamide
wQED
MW
AlogP
HBA
HBD
TPSA
nRB
SAlerts
nAtomRing
wQED
Lithospermoside amide
347
-3.3
10
7
183
4
1
0
0.29
Lithospermoside acid
348
-2.9
10
7
177
4
1
0
0.31
uwQED (tabl.80) and wQED (Tabl 81) of a potential pharmaceutical form including amide and
carboxylic acid, obtained by hydrolysis of the nitrile group of Lithospermoside meets the requirements for
conservative treatment.
4.1.16.3. Conclusion from the part
The application of the methodological scheme from §3.1.1.3 for a potential pharmacological form
(§4.1.16), proves maximum qualification for oral medicinal products. No toxicity deviations were observed
and the values were respectively: Oral rat LD50 [mg/kg] for amide 5016 ≤ 13956 ≤ 38832, acid 4015 ≤ 10006
≤ 24938 and Bioaccumulation factor [conditional units] amide 0.86 ≤ 14 ≤ 228, acid 0.00 ≤ 0.25 ≤ 567.
4.2. Determination of the drug dose
The drug dose is determined by considering all possible substances obtained by the final hydrolysis of
the glycosidic bond inside the cancer cell (Table 82).
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Tabl. 82. Nature and concentration of active anticancer cell molecules forms obtained after crossing the cell
membrane by their natural precursors
chemical formula of
AACF obtained after
crossing the cell
membrane
natural precursor modified and
treated with amide and
carboxylic acid enzyme
hydrolysis
AACF concentration
derived from the 1 mg / ml
pharmacological
formulation [mg/ml]
Prunasin 4.13:1
Amygdalin 4.87:1
Lucumin 4.91:1
Vicianin 4.74:1
Sambunigrin 4.09:1
0.39
0.26
0.29
0.28
0.39
Dhurrin 4.13:1
Taxiphyllin 4.33:1
Proteacin 4.67:1
p-Glucosyloxymandelonitrile 4.61:1
0.40
0.42
0.28
0.42
Zierin 4.02:1
0.40
Linamarin 3.94:1
0.31
Lotaustralin 4.41:1
0.34
Acacipetalin 4.34:1
0.34
Triglochinin 4.91:1
0.47
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Deidaclin 4.08:1
Tetraphyllin A 4.17:1
0.36
0.36
Tetraphyllin B 4.11:1
Volkenin 4.29:1
Taraktophyllin 4.23:1
0.37
0.39
0.39
Gynocardin 4.32:1
0.40
Menisdaurin 4.53:1
0.43
Epiheterodendrin 4.39:1
0.34
Griffonin 4.76:1
0.44
Bauhinin 4.27:1
0.44
Purshianin 4.32:1
0.41
Lithospermoside 4.15:1
0.43
The use of two or more pharmaceutical forms would not prevent their penetration subject to the mass
ratios between the active antitumor amide and the active carboxyl transfer form.
The chemical compounds listed in Table 82 and are currently used as: anti-migrane, anti-atherosclerotic,
anticoagulant, treatment of HIV, anti-cancer, anti-asthmatic, anti-hypertensive, anti-epileptic, analgesic,
ocular anti-inflammatory, anti-hypertensive, hypnotic, anesthetic, anti-allergic, aromatase inhibitor, anti-
ulcerative, anti-neoplastic, antibacterial, anticoccidial, contraceptive, tyrosine-kinase inhibitor treatment of
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mast cell tumors, etc.. The difference is that with the proposed technology they are formed inside the cell itself
and thus minimize their overall toxicity in the body.
5. CONCLUSION
The known cellular reactions (§ 1), which in this case are a function of one of the fundamental principles
of medical chemistry - "structure-activity", define conclusions that give some of the scientific answers on the
topic "Theoretical analysis of anticancer cellular effects of glycosamidamides":
1) Amides resulting from the hydrolysis of nitrile glycosides would have the ability to cross the cell
membrane of a cancer cell and thus cause its cellular response;
2) The pharmaceutical form must represent the exact amide / carboxylic acid ratio for the corresponding
active anticancer cell form;
3) Clinical concentrations are more than seven times higher than those of nitrile glycosides due to their
reduced toxicity;
4) No process is observed, preventing the use of several pharmaceutical forms together and / or
sequentially.
ETHICS APPROVAL AND CONSENT TO PARTICIPATE
Not applicable.
HUMAN AND ANIMAL RIGHTS
No Animals/Humans were used for studies that are the basis of this research.
CONSENT FOR PUBLICATION
Not applicable.
AVAILABILITY OF DATA AND MATERIALS
The authors confirm that the data supporting the findings of this study are available within the article.
FUNDING
None.
CONFLICT OF INTEREST
The authors confirm that this article content has no conflict of interest.
ACKNOWLEDGEMENTS
Declared none.
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