In silico Assessment of Factor Xa Inhibitors by Docking Studies

Abstract

Human Factor Xa (FXa), a blood coagulation enzyme which catalyses the activation of prothrombin to thrombin and plays a pivot role in haemostasis and thrombosis. Imbalance in the activation of this enzyme disturbs the normal haemostasis leading to bleeding disorders and also vascular occlusion with overproduction of thrombin. This intravascular clot formation causes many cardiovascular diseases such as acute myocardial infarction (AMI), stroke, pulmonary embolism (PE), and deep vein thrombosis (DVT). So the direct inhibition of FXa may contribute for developing effective and safe anticoagulants without effecting thrombin activity necessary for normal hemostasis. The present study initiates to  provide insight of FXa inhibition and facilitate the design of more potent ligands , a series of Sulfonamide and Thiophene-Anthranilamide derivatives are docked to the X-ray structure of FXa(2P95) using Discovery Studio(DS), and their binding conformations are analyzed. The docking analysis shows the compound 1v (2-(5-Chloro-2-thienyl)-N-{(3S)-1-[(1S)-1-methyl-2-(4-morpholinyl)-2-oxoethyl]-2-oxo-3-pyrrolidinyl}-1,3-thiazole-5-sulfonamide) of sulfonamide derivatives and 12b(3-Chloro-N-[4-chloro-2-[[(5-chloro-2-pyridinyl)amino]carbonyl]-6-methoxyphenyl]-4-[[methyl(methylsulfonyl)amino]methyl]-2-thiophenecarboxamide)of Thiophene-Anthranilamides are having a high dock score of 55.722K.Cal/mol and 57.523 K.Cal/mol respectively, may act as potent inhibitors of FXa for the development of antithrombotic drugs.