MOLECULAR DOCKING ANALYSIS OF 3- SUBSTITUTED 5-HYDROXY COUMARIN DERIVATIVES AS VITAMIN K EPOXIDE REDUCTASE INHIBITORAbstract
Warfarin and coumarin containing drugs act on Vitamin K epoxide reductase to show its anti-coagulant activity. In this study, three different series of 5- hydroxy 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.
Ashwini M. Londhe* and Anuruddha R Chabukswar
Pharmaceutical Chemistry Department, Maeer’s Maharashtra Institute of Pharmacy, Ex-Serviceman Colony, Kothrud, Pune-411038, Maharashtra, India
04 September, 2014
13 November, 2014
06 January, 2015
01 May, 2015