Theoretical Analysis of Anticancer Cellular Effects of Glycoside Amides.

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 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-oxoethylide ne)hex-2-enedioic acid, (S)-1-hydroxycyclopent-2-ene-1-carboxamide, (1S,4S)-1,4-dihydroxycyclopent-2-ene-1-carbox amide, (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.

Theoretical Study of the Process of Passage of Glycoside Amides through the Cell Membrane of Cancer Cell.

BACKGROUND: This article concentrates on the processes occurring in the medium around the cancer cell and the transfer of glycoside amides through their cell membrane. They are obtained by modification of natural glycoside-nitriles (cyano-glycosides). Hydrolysis of starting materials in the blood medium and associated volume around physiologically active healthy and cancer cells, based on quantum-chemical semiempirical methods, are considered. OBJECTIVE: Based on the fact that the cancer cell feeds primarily on carbohydrates, it is likely that organisms have adapted to take food containing nitrile glycosides and/or modified forms to counteract "external" bioactive activity. For their part, cancers have evolved to create conditions around their cells that eliminate their active apoptotic forms. This is far more appropriate for them than changing their entire enzyme regulation to counteract it. In this way, it protects itself and the gene sets and develops accordingly. METHODS: Pedestal is derived that closely defines the processes of hydrolysis in the blood, the transfer of a specific molecular hydrolytic form to the cancer cell membrane and with the help of time-dependent densityfunctional quantum-chemical methods, its passage and the processes of re-hydrolysis within the cell itself, to bioactive forms causing chemical apoptosis of the cell-independent of its non-genetic set, which seeks to counteract the process. RESULTS: Used in oncology, it could turn a cancer from a lethal to a chronic disease (such as diabetes). The causative agent and conditions for the development of the disease are not eliminated, but the amount of cancer cells could be kept low for a long time (even a lifetime). CONCLUSION: The amide derivatives of nitrile glycosides exhibit anticancer activity; the cancer cell probably seeks to displace hydrolysis of these derivatives in a direction that would not pass through its cell membrane and the amide-carboxyl derivatives of nitrile glycosides could deliver extremely toxic compounds within the cancer cell itself and thus block and/or permanently damage its normal physiology.

Theoretical Analysis for the Safe Form and Dosage of Amygdalin Product.

Indroduction: This article presents a theoretical analysis of the safe form and dosage of the amygdalin derivative. By making a precise socio-anthropological analysis of the life of the ancient people of Botra (Hunza people, Burusho/Brusho people), a hypothesis has been postulated through a number of modern quantum-mechanical, molecular-topological and bio analytical checks, and has also been confirmed by two proofs. METHODS: The proposed hypothesis underwent theoretical and logical analysis to confirm and/or reject it. The methodological scheme was: determining the optimal chemical formula, determination of the pharmaceutical molecular form and determination of the drug dose. RESULTS: A convenient, harmless, form of amygdalin derivative is available that has the same biological and chemical activity and could be used in conservative clinical oncology. The article also presents a theoretical comparative analysis of biochemical reactivity in in vivo and in vitro media, by which we also determine the recommended dosage for patient administration. A comparative analysis of the data, obtained in published clinical studies of amygdalin, is presented, summarizing a scheme of the anti-tumor activity of the proposed molecular form. CONCLUSION: The hydrolyzed to amide / carboxylic acid cyano / nitrile glycosides are potential drugs. Their biological activity remains unchanged, but their toxicity is many times lower than unmodified native molecules. We claim that this study we have conducted on amygdalin / dhurrin-derived amide is the only study on this molecular form. Other substances in these groups with pronounced biological activity (including anti-tumor) are the hydrolyzed nitrile groups by Prunasin, Lucumin, Vicianin, Sambunigrin, Dhurrin, Taxiphyllin, Zierin, Preteacin, p-Glucosyloxymandelonitrile, Linamarin, Lotaustralin, Acaciapetalin, Triglochinin, Dejdaclin, Tetraphyllin A, Tetrallin B, Gynocardin etc., to their amide/carboxylic acid.