INFLUENCE OF QUINAZOLINONE-4 DERIVATIVES ON A BLOOD COAGULABILITY

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Purpose of the work: the evaluation of the influence of synthesized biologically active compounds - derivatives of quinazolinone-4 on blood coagulability. Materials and methods of the study: we have studied 2 excipients - derivatives of quinazolinone-4 (laboratory codes: PFI-1, PFI-6; provided by the department of organic chemistry of Pyatigorsk Medical and Pharmaceutical Institute - a branch of Volgograd State University). Experimental animals - adult male and female Wistar white rats weighed 220-250 g (in groups by 5-6 animals), were kept in the conditions of natural illumination, standard temperature, free access to water and food in the university’s vivarium according to the recommendations of a national standard RF GOST P-53434-2009 “Principals for a proper laboratory practice.” We studied the influence of substances at doses 2/10 from a mol-mass in mg/kg: PFI-1 - 47.6 mg/kg, PFI-6 - 59.2 mg/kg (doses were selected considering the analysis of the literature data). The solutions of the excipients under study, solubilized in the presence of tween-80, were injected abdominally during 7 days once a day on a certain time. Control groups of male and female rats were given with 0.4 ml of tween-80 solution abdominally (1-2 drops on 10 ml of water) in similar regimes. The experiments were conducted during day time. The influence of the substances under study on blood coagulability was evaluated by the time of blood flow cease from the tip of a tail of an animal. The data obtained were processed statistically with a standard computer program package with the evaluation of normality of distribution following Shapiro-Wilk W-statistics. Statistically significant parametric differences were revealed by using Student’s criterion, non-parametric criteria of Kruskal-Wallis, Mann-Whitney, Wilcoxon. Results: following the results of the tests we have established that after the chronic administration of PFI-1 excipient to female rats the time of blood flow cease expanded by 25% in relation to the level of a control group of male rats, which were given with a solvent (taken for 100%). Consequently, it is possible to suppose the expansion of antithrombogenous (anticoagulant/ antiaggregant / thrombolytic) action of the PFI-1 substance. Chronic use of PFI-6 excipient was accompanied by a decrease of bleeding cease time by 40% comparing with control level of female rats group, which were given with the solvent (taken for 100%). Hemostatic influence of the substance under study was manifested. Conclusions: thus, the studied excipients, biologically active compounds - derivatives of quinazolinone-4 influence blood coagulability. PFI-1 compound exhibits antithrombogenous (anticoagulant/ antiaggregant / thrombolytic) action, and PFI-6 substance has a hemostatic action. We consider prospective the further researches of “dose-activity” dependence for the studied substances and possible mechanisms of influence on coagulant and anticoagulant blood systems. The further search for compounds which influence the aggregation of thrombocytes, blood coagulability, and fibrinoliz together with new synthesized biologically active substances - derivatives of quinazolinone-4 are also of great interest.