MOLECULAR DOCKING STUDIES OF INDENOISOQUINOLINE DERIVATIVES WITH DNA-TOPOISOMERASE I COMPLEX

The aim of the present study is to find the effectiveness of two series of indenoisoquinolines compounds against cancer. Topoisomerase I (Top 1) an essential enzyme that participates in the processes associated with separation of DNA strands and manages the super helical tensions through the transient breakage of one strand of duplex DNA, monitored by the unwinding of supercoiled DNA. The Top 1-DNA complex an effective target in the treatment of cancer was taken as a receptor for study. The two series of indenoisoquinolines compounds were taken as ligand molecules and the 3D structure of human Top1-DNA was retrieved from PDB database. The structures of ligand were drawn using Chemsketch. Docking studies were performed using GOLD which predicts the binding affinity and hydrogen bond interactions between the ligand and receptor. From the results, it was observed that the selected series of both nitrated indenoisoquinolines and 2, 3 dimethoxy-substituted indenoisoquinolines had better Gold score with the active site residue ARG364. Docking studies conclude both the series may act as potent inhibitor that can be further studied for developing anticancer agents.