MOLECULAR DOCKING ANALYSIS OF 3-SUBSTITUTED 5-HYDROXY COUMARIN DERIVATIVES AS VITAMIN K EPOXIDE REDUCTASE INHIBITOR

Warfarin and coumarin containing drugs act on Vitamin K epoxide reductase to show its anti-coagulant activity. In this study, three different series of 5hydroxy coumarin containing phenyl, furan and pyran substituents at third position were designed. Molecular docking studies were performed to determine binding modes and affinities of ligand molecule towards Vitamin K epoxide reductase. In docking studies pair wise linear potential (PLP score) was used as a scoring function and systematic search method to find out bio active conformer. Ligand 2B, 2C, 2D, 2E, 3C, 3D has shown more negative binding energies, which reflects its affinity towards a vitamin K epoxide reductase. Ligand 1A, 1E, 3D has shown maximum hydrogen bond interactions as compared to warfarin. Tyr178, Thr72, Met111, Glu115amino acid residues were involved in the ligand-protein interactions. Hydroxy, methoxy, ethoxy and methyl substitutions has played major roles in the ligand-protein interaction. Therefore, 3-substituted -5-hydroxy coumarins could be served as good drug candidates for anticoagulant activity and additional experimental studies are warranted to locate their importance as anticoagulant.