Synthesis and Antiplatelet Potential Evaluation of 1,3,4-Oxadiazoles Derivatives

Abstract

Abstract A novel series of 2-(3-methyl-1,6-diphenyl-1H-pyrazolo[3,4-b]pyridin-4-yl)-5-aryl-1,3,4-oxadiazoles (4a–4h) has been synthesized from corresponding hydrazones (3a–3h) and evaluated their antiplatelet aggregation effect induced by arachidonic acid and collagen. Spectral data and elemental evaluation were used to confirm the structure of the compounds while molecular docking against cyclooxygenase 1 and 2 (COX1 & COX2) and quantitative structure-activity relationship (QSAR) were performed in describing their antiplatelet potential. All synthesized compound exhibited more than 50% platelet aggregation inhibition against both arachidonic acid and collagen. Antiplatelet activities results showed that 4b and 4f compounds have highest % inhibition against arachidonic acid. High Egap and ionization potential values showed that the compound 4d, 4e and 4f were supposed to be more active and good electron donor while 4b, 4c, 4d, 4e, 4g and 4h might be more active due to more electrophilic sites. Interaction with more than one residues in the binding pocket of COX-1 in comparison with aspirin and ligand efficacy (LE) consequences showed that compounds have excellent action potential for COX-1. Computational evaluations are in good agreement with antiplatelet activities of the compounds. All compounds might be promising antiplatelet agents especially 4b, 4f and helpful in the synthesis of new drugs for the treatment of cardiovascular diseases (CVDs).