APPROBATION OF CALIX[4]ARENE AS AN ANTITHROMBOTIC AGENT IN VIVO

Abstract

Intravascular thrombosis is one of the main causes of mortality in the working-age population of the world. There are no antithrombotic drugs that act directly on the final stage of thrombosis – fibrin polymerization. However, a new compound of the calix[4]arene series, calix[4]arene C-145, which directly interacts with the fibrin polymerization site ‘A-knob’ thus blocking formation of polymeric fibrin and preventing thrombosis. So, the purpose of this work was to study the calix[4]arene C-145 series as antithrombotic agents in vivo using different animals and types of administration. Materials and methods. Laboratory animals (rats, mice and rabbits) were used for C-145 testing in vivo. Activated partial thromboplastin time and platelet aggregation were measured to determine the anticoagulant action after intravenous or per os administration. Results. Per os way of administration was selected as the optimal one. We showed the substantial prolongation of clotting time in APTT test that was observed starting from the 2nd hour after the per os administration, reached the maximum on 6th hour and eliminated in 24 hours. The effect of C-145 on platelets reached maximum on 4-6 hours and eliminated in 12 hours. Conclusions. C-145 was proven to be prospective antithrombotic drug that can be administered per os. Further investigations must be focused on the study of C-145 pharmacodynamics and metabolism. Such data would allow fast implementation of the tested compound into practice.