Tricyclic benzimidazoles as potent poly(ADP-ribose) polymerase-1 inhibitors

Novel tricyclic benzimidazole carboxamide poly(ADP-ribose) polymerase-1 (PARP-1) inhibitors have been synthesized. Several compounds were found to be powerful chemopotentiators of temozolomide and topotecan in both A549 and LoVo cell lines. In vitro inhibition of PARP-1 was confirmed by direct measurement of NAD(+) depletion and ADPribose polymer formation caused by chemically induced DNA damage.