Inhibitory Mechanism Exhibited by Phenol-based Natural Products against DNA Polymerase alpha from Psoralea corylifolia by Molecular Docking

Natural products play a significant role in the design of anticancer drugs acting on DNA replication. Different classes of natural products include meroterpene, phenol, flavonoid and coumestan isolated from Psoralea corylifolia plant have been found active against cancer disease. DNA polymerase and topoisomerase are the important reported targets for cancer chemotherapy. In the present work, docking analysis of total fifteen different phenol-based (1-12) and furanocoumarin-based (13-15) natural products from P. corylifolia were studied against DNA polymerase alpha. The objective of this study was to find the potential binding residues of phenol-based inhibitors against DNA polymerase alpha. In the light of docking results, it can be suggested that crucial interactions of inhibitor's phenolic group with the amino acid residues of DNA polymerase alpha are responsible for their activity. In particular, hydrogen bond interaction between phenol-based natural products with the carboxylate oxygen of Asp1004 residue is of prime importance as the mutated enzyme has no polymerase activity at all. Moreover, hydrophobic and pi-pi stacking interactions between phenol-based inhibitors and Tyr865, DG110, DG111, and DC11 side chains of DNA polymerase alpha are also observed which may play an additional role. It is further elucidated that furanocoumarin-based natural products did not show any significant interaction with the ASP1004 due to the absence of phenolic OH group. Docking results disclose the reason behind the activity of phenol-based and inactivity of furanocoumarin-based natural products against DNA polymerase alpha.