RESEARCH OF CERTAIN TOXICO-KINETIC PARAMETERS OF THE SERIES OF 2-(2-(7-ALKYL-1,3-DIMETHYL-2,6-DIOXO-2,3,6,7-TETRAHYDRO-1H-PURINE-8-YL) HYDRAZONO)SUCNIC ACIDS

Abstract

Introduction. Preliminary assessment of potential pharmacological properties and toxicity of the relevant compounds is an important stage in the development of new active pharmaceutical ingredients. It allows to determine their therapeutic potential, as well as possible negative impact on humans, animals, plants and the environment.For example, known xanthine (2,6-dioxopurine) derivatives have been shown to exert significant effects on the body, including bronchodilatory, cardiotonic, diuretic, anti-aggregant, antioxidant, and antitumor activities.This clearly confirms the promise of further research aimed at developing new pharmaceutical substances based on this heterocycle.The aim of the study – to conduct a series of in silico tests of virtual compounds – purine derivatives: 2-(2-(7-alkyl-1,3-dimethyl-2,6-dioxo-2,3,6,7-tetrahydro-1H-purine-8-yl)hydrazono)succinic acids to determine their individual toxico-kinetic parameters.Research Methods. In silico methods for predicting pharmacological activity, side and toxic effects, carcinogenicity, half-lethal dose, metabolism, druglikeness parameters.Results and Discussion. Screening researches have shown that all substances in the virtual library are highly likely to exhibit antihypertensive effects due to peripheral vasodilation. The lead compound is a methyl derivative at the 7-position. The introduction of a branched alkyl fragment into the molecular structure slightly reduces the likelihood of exhibiting all types of pharmacological activity. The compound with an ethyl substituent at the 7-position has the highest probability of being a potential ATP protease inhibitor. The tested compounds do not exhibit hepatotoxic or cardiotoxic effects; however, there is a probability of developing respiratory toxicity. They belong to toxicity class 4, meaning they are relatively low-toxic. All substances in the virtual library demonstrate good water solubility, ensuring the necessary pharmaco-technological properties. It was determined that upon entering the body, they will undergo phase I biotransformation. The model compounds meet Lipinski's rule (a sufficiently high level of drug similarity has been established).Conclusions. Virtual substances of the series of 2-(2-(7-alkyl-1,3-dimethyl-2,6-dioxo-2,3,6,7-tetrahydro-1H- purine-8-yl)hydrazono)succinic acids are likely to exhibit antihypertensive effects due to peripheral vasodilation according to the results of in silico researches; they are low-toxic substances, soluble in water; they meet Lipinski's rule. The leading compounds are molecules with methyl and ethyl fragments in the 7-position.