Design, Synthesis, Docking Study and Antiplatelet Evaluation of New Thiosemicarbazide Derivatives Derived from Captopril

Abstract

A series of thiosemicarbazide derivatives of captopril, a well-known angiotensin-converting enzyme inhibitor ACEI, have been synthesized by reaction of hydrazide of captopril with different phenylisothiocyanate substituents. The synthesized compounds were characterized using FTIR, 1HNMR and CHNS analysis. The final derivatives were tested for antiplatelet activity using multiplate analyzer and adenosine diphosphate (ADP), arachidonic acid (AA), and collagen, as platelet aggregation inducers. Among tested compounds, derivative 7 and 10 were the most potent inhibitors of platelet aggregation induced by arachidonic acid, with percent inhibition (97.14±0 and 95.71±2.02) and IC50 (2.7 and 1.21μgml), respectively. Molecular docking study was performed using purino receptor P2Y12, COX-1, and glycoprotein llbllla as the target protein, compound 7 has a potential to become as a lead molecule for COX-1 inhibitor with binding energy (-10.67) Kcal/mol. Also, compound 6 was found as the best inhibitor for the glycoprotein IIa/IIIb with percent inhibition (83.9±2.8), and binding energy (-10.05) Kcal/mol.