Structure-based design of new poly (ADP-ribose) polymerase (PARP-1) inhibitors

Poly (ADP-ribose) polymerase (PARP-1) is a well-established nuclear protein with prominent role in signaling and DNA repair. Various clinical candidates have been identified with the role in PARP-1 inhibition. Based on the pharmacophoric features identified from previous studies and molecular docking interactions, thiazolidine-2,4-dione derivatives have been evaluated for their PARP inhibitory activity. From an in vitro assay, 5-((1-(4-isopropylbenzyl)-1H- indol-3-yl) methylene) thiazolidine-2,4-dione (16) was identified as a potent inhibitor having low micromolar inhibitory activity (IC50 = 0.74 +/- 0.25 mu M). Thus, a structure-based design approach utilized in the present study helped to identify thiazolidine-2,4-dione as a novel scaffold against PARP-1 for potential development of potent anticancer therapeutics.