ANTICOAGULATION ACTIVITY OF 6-METHYLURACIL HYDRAZONE DERIVATIVES INCLUDING A FOUR-MEMBER SULFUR-CONTAINING CYCLE WITH DIFFERENT DEGREE OF SULFUR ATOM OXIDATION

Abstract

Abstract: Aim: Data on the chemical structure of biologically active compounds show that various antibacterial, antiviral, antitumor, anticoagulant, and other agents contain heterocyclic systems. However, at this stage in the development of medicine and pharmacy, thrombosis and thromboembolic complications remain one of the key causes of morbidity and mortality on a global scale. Therefore, the search for new anticoagulants is an urgent trend in pharmaceutical chemistry and pharmacy in general. Purpose: The purpose of our experiment was to synthesize new biologically active compounds and screen the obtained substances for anticoagulant activity. Materials and Methods: The synthesis of new compounds was carried out according to the methods developed by us. The structure of the obtained biologically active substances was confirmed by 1H NMR spectroscopy. The individuality of the compounds was monitored by TLC. Preliminary in silico screening of the synthesized substances was performed on the Way2Drag platform. Experimental data on anticoagulant activity were recorded in vitro on the blood of healthy male donors aged 18-24 years. For screening, solutions of substances were selected that did not sediment within 2 hours of settling at room temperature after dissolution. In addition to control indicators for the studied solutions, data were recorded when the isovolumic volume of the solvent was added to exclude its effect on the hemostatic system. The data obtained were processed using the statistical package Statistica 10.0 (StatSoft Inc, USA). The normal distribution of the actual data was checked using the Shapiro-Wilk test. Conclusions: Methods for the synthesis of new compounds based on 6-methyluracil have been developed. Screening of the anticoagulant activity of the obtained substances was carried out. New potential anticoagulants have been identified.