Insight into the binding of a synthetic nitro-flavone derivative with human poly (ADP-ribose) polymerase 1

Flavones are important bioactive compounds, many of which are effective in cancer therapy for their ability to target enzymes related to DNA repair and cell proliferation. In this report, the interaction of a synthetic nitroflavone, 2,4-nitrophenylchromen-4-one (4NCO) with human poly (ADP-ribose) polymerase 1 (hPARP1) was investigated to explore its inhibitory action. Its interaction with hPARP1 was compared with that of other inhibitors through molecular docking studies. Further insight into the 4NCO-hPARP1 interaction was obtained from competitive docking and molecular dynamic simulation studies. In silico mutagenesis studies and per-residue interaction energy calculations were carried out. Quantitative Structure Activity Relationship analysis was also performed to calculate its predictive percent inhibitory activity. Our results indicated that 4NCO exhibited competitive mode of binding to hPARP1. It formed a stable interaction with the protein thereby hindering any further molecular interaction to render it inactive with a predictive inhibition of 96%. It also had good ADMET properties and showed best Autodock binding free energy values compared to other known inhibitors. 4NCO showed good hPARP1 inhibitory properties with higher bioavailability and lower probability of getting effluxed. Development of inhibitors against hPARP1 is important for cell proliferative disorders, where 4NCO can be predicted as a potential new drug.