Molecular Docking Study of Coumarin Derivatives Binding to Caspase-7, a Key Player in the Apoptosis Pathway

This study is focused on analysis of inhibitory activity of novel molecules in the active site of human caspase-7. Caspase inhibition is an approach for treating multiple diseases such as Osteoarthritis, Alzheimer's disease, Parkinson's disease and Cisplatin induced renal injury. The caspase family of proteins, particularly activated caspase 3, 7 and 8, is widely implicated in cisplatin induced tubular cell apoptosis. Caspase-7 is a popular drug target for Cisplatin induced renal injury. Coumarins are a family of natural compounds with anti-cancer, anti-inflammatory, anti-oxidant and many more therapeutic properties. Coumarin derivatives were used as the ligands for the caspase-7 receptor using a molecular docking approach. The crystal structure of caspase-7 was obtained from the protein data bank, entry 4FDL, and a set of coumarin derivatives were docked in to the pre-equilibrated protein structure using AutoDockVina and Gold software. The interaction diagrams were obtained using BIOVIA discovery studio. Hydrogen bonds and pi-stacking interactions were considered favorable for stabilizing the ligand in the active site. Results revealed that there are favorable interactions with coumarin derivatives used in this study and caspase-7. The coumarin derivatives with high binding affinity may be developed as potential drug candidates.