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 [Formula: see text]. 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.