Recent Progress in the Research on Benzimidazole PARP-1 Inhibitors.

Poly (ADP-ribose) polymerase-1 (PARP-1) is a multifunctional protein that plays an important role in DNA repair and genome integrity. PARP-1 inhibitors can be used as effective drugs not only to treat BRCA-1/2 deficient cancers because of the synthetic lethality effect but also to treat non- BRCA1/2 deficient tumours because of the effect of PARP capture. Therefore, PARP inhibitors have become a focus of compelling research. Among these inhibitors, substituted benzimidazole derivatives were mainly concerned as lead compounds. However, the commercially available benzimidazole PARP-1 inhibitors have some shortcomings, such as serious toxicity in combination with chemotherapy drugs and in vivo cardiovascular side effects such as anemia. Therefore it is crucial for scientists to explore more structure-activity relationships of the benzimidazole PARP-1 inhibitors and access safer and more effective PARP inhibitors. As the binding regions of PARP-1 and the substrates are usually characterized by NI site and AD site, the modification of benzimidazoles mainly occurs on the benzimidazole skeleton (NI site) and the side chain of benzimidazole in the 2-C position (AD site). Herein, the recent progress in the research on benzamides PARP inhibitors was introduced. We noticed that even though many efforts were made to the modification of NI sites, there was still a lack of optimistic and impressive results. However, the structure-activity relationships of the modification of AD sites have not been thoroughly discovered yet. We hope that enlightened by the previous research, more research on AD sites should be carried out, and more effective benzimidazole PARP-1 inhibitors could be designed, synthesized, and applied to clinics.