Computational evaluation of certain flavonoids against poly (ADP-Ribose) Polymerase-1 using in silico docking studies

In silico evaluation of PARP-I

Abstract

Poly (ADP-Ribose) Polymerase-1 ( PARP-1) inhibitors may represent a class of chemotherapeutic mediators at cancers with defective DNA-damage repair. The objective of the present study is to examine the inhibitory affinity potential of the certain commercially available flavonoids such as acacatechin, catechin, daidzein, galangin, and kaempferol against PARP-1 enzyme using in silico docking studies. The in silico docking studies were performed using AutoDock 4.2. Olaparib, a known PARP-1 inhibitor was used as standard. In the docking studies, the conformational site analysis and the docking parameters were evaluated for the flavonoids against the PARP-1. The selected flavonoids showed excellent theoretical pharmacokinetic properties and no violations were described against Lipinski Rule of 5. Further the flavonoids were subjected to molecular docking analyses. The docking energy and other parameters demonstrated that the flavonoids are highly conserved in nature. The top ranking molecule catechin has a minimum energy score of -6.55 kcal/mol. The amino acid residues responsible for the PARP-1 inhibition of the catechin were found to be Lys 15, Ser 108, and Gly 109. This compound is thus a good leading point for further development of strong inhibitors against PARP-1 enzyme, which might be attributed to the presence of benzopyran ring in its structure. Hence, further examination is required to develop novel chemical entities for the prevention and management of ovarian and breast cancer.