ANTIAGGREGATIONAL AND DISAGGREGATIONAL ACTIVITY OF NEW SULFUR-CONTAINING URACIL DERIVATIVES

Abstract

Aim: Treatment and prevention of various pathologies of hemostasis and the search for biologically active substances with anti-aggregation and disaggregation effects are one of the main lines of relieving pathogenic conditions of ischemia. The duration of the onset of the therapeutic effect, the risk of bleeding, a decrease in the number of platelets and neutrophils, allergic manifestations - this is not a complete list of the side effects of current antiplatelet agents; in addition, with long-term use, the development of resistance occurs. Such conclusions accelerate and stimulate new research into the search for a new generation of antiplatelet agents, not only characterized by a reduction in side effects, but also targeted ones. Purpose: The purpose of the research directs to analyze the antiaggregatory and disaggregatory activity of the first synthesized sulfur containing uracil derivatives. Materials and Methods: New derivatives were synthesized as a result of the alkylation reaction of pyrimidine derivatives with 2-chloromethylthiirane. The structure of the obtained biologically active substances was confirmed using standardized methods of physicochemical analysis. Individuality was controlled by thin layer chromatography. Quantitative in silico analysis of putative activities of novel compounds was performed on the Way2Drag platform. To conduct in vitro experiments, blood was collected from 27 healthy male donors. The studies were carried out by first dissolving samples of compounds in DMSO. Solutions that sediment at room temperature after settling for 1.5-2 hours was not allowed for study. All solutions were stored in a refrigerator for no more than 24 hours from the date of dilution, at a temperature not exceeding +8 °C. An additional control group consisted of tests that were exposed to an equivolume amount of solvent. The reference drug used was the standard 2-(acetyloxy)benzoic acid (“Acetylsalicylic acid”, Shandong Xinhua Pharmaceutical Co., Ltd., China). The obtained data were processed using the statistical package Statistica 10.0 (StatSoft Inc, USA). Testing for normal distribution of actual data was performed using the Shapiro-Wilk test. Conclusions: Methods for the synthesis of new uracil derivatives have been developed. The antiaggregation and disaggregation activity of the obtained substances was analyzed. New potential antiplatelet agents have been identified.