Poly (ADP-ribose) polymerase (PARP) inhibitors as anticancer agents: An outlook on clinical progress, synthetic strategies, biological activity, and structure-activity relationship.

ABSTRACT

Poly (ADP-ribose) polymerase (PARP) is considered an essential component in case of DNA (Deoxyribonucleic acid) damage, response by sensing DNA damage and engaging DNA repair proteins. Those proteins repair the damaged DNA via an aspect of posttranslational modification, known as poly (ADP-Ribosyl)ation (PARylation). Specifically, PARP inhibitors (PARPi) have shown better results when administered alone in a variety of cancer types with BRCA (Breast Cancer gene) mutation. The clinical therapeutic benefits of PARP inhibitors have been diminished by their cytotoxicity, progression of drug resistance, and limitation of indication, regardless of their tremendous clinical effectiveness. A growing number of PARP-1 inhibitors, particularly those associated with BRCA-1/2 mutations, have been identified as potential cancer treatments. Recently, several researchers have identified various promising scaffolds, which have resulted in the resuscitation of the faith in PARP inhibitors as cancer therapies. This review provided a comprehensive update on the anatomy and physiology of the PARP enzyme, the profile of FDA (Food and Drug Administration) and CFDA (China Food and Drug Administration)-approved drugs, and small-molecule inhibitors of PARP, including their synthetic routes, biological evaluation, selectivity, and structure-activity relationship.