Synthetic PARP-1 Inhibitors Reported During the Last Decade

Background Cancer is the world's second-largest cause of death, and is responsible for an estimated 9.6 million mortality cases in 2018. Poly-ADP-ribose polymerases (PARPs) are enzymes and a family of proteins involved in many cellular processes, including DNA repair, gene regulation, chromatin remodeling, and apoptosis. The first characterized and best-known member of the PARP family is poly(ADP-ribose) polymerase 1 (PARP-1). PARP-1 is a major protein for DNA single-strand breaks in the BER pathway (base excision repair) (SSBs). Objective The objective of this article was to compile synthetic PARP-1 inhibitors reported in the last decade. Methods In the present manuscript, bibliographic investigation was carried out by scrutinizing peer-reviewed articles from online/offline databases. The inclusion criteria consisted of the most relevant studies indicating the relationship between PARP-1 and cancer in textbooks/edited books and peer-reviewed papers from scientific databases, like SCOPUS, PUBMED, NISCAIR, and Google Scholar since 2010 to 2020. Only the studies published in English language were searched/considered. The exclusion criteria consisted of the studies on other PARP isoforms than PARP-1. The studies thus obtained were classified according to the heterocyclic moieties, year of publication, etc. The data compiled in this article is a systematic review of the reported studies. Results The literature reports indicated that a number of PARP-1 inhibitors reported have IC50 value in nanomolar concentration. Conclusion PARP-1 is an essential target for anti-cancer drug discovery. Further research on more effective and safe PARP-1 inhibitors needs to be carried out, and we may discover some novel PARP-1 inhibitors in the near future.

Automated summary

Background: Cancer is the second-leading cause of death worldwide, with an estimated 9.6 million deaths in 2018. PARP-1 is an enzyme and protein family involved in various cellular processes, including DNA repair and gene regulation. This article summarizes synthetic PARP-1 inhibitors reported in the past decade and highlights the need for further research on effective and safe PARP-1 inhibitors for cancer treatment.