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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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The active anti-cancer pharmaceutical forms are more than 70. The full list is located in: DOI: 10.5281/zenodo.13777292
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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.