Molecular Docking, Computational, and Antithrombotic Studies of Novel 1,3,4-Oxadiazole Derivatives

Abstract

A new series of 1,3,4-oxadiazoles derivatives was synthesized, characterized, and evaluated for their in vitro and in vivo anti-thrombotic activity. Compounds (3a⁻3i) exhibited significant clot lysis with respect to reference drug streptokinase (30,000 IU), and enhanced clotting time (CT) values (130⁻342 s) than heparin (110 s). High affinity towards 1NFY with greater docking score was observed for the compounds (3a, 3i, 3e, 3d, and 3h) than the control ligand RPR200095. In addition, impressive inhibitory potential against factor Xa (F-Xa) was observed with higher docking scores (5612⁻6270) with Atomic Contact Energy (ACE) values (−189.68 to −352.28 kcal/mol) than the control ligand RPR200095 (Docking score 5192; ACE −197.81 kcal/mol). In vitro, in vivo, and in silico results proposed that these newly synthesized compounds might be used as anticoagulant agents.

Keywords

• factor Xa (F-Xa)
• cardiovascular diseases (CD)
• coronary heart disease (CHD)
• tissue plasminogen activator (t-PA)
• urokinase (UK)
• streptokinase (SK)
• <i>N</i>,<i>N</i>-dimethyl formamide (DMF)