Discovery of pyrano[2,3-d]pyrimidine-2,4-dione derivatives as novel PARP-1 inhibitors: design, synthesis and antitumor activity.

ABSTRACT: Poly(ADP-ribose) polymerases-1 (PARP-1) are involved in DNA repair damage and so PARP-1 inhibitors have been used as potentiators in combination with DNA damaging cytotoxic agents to compromise the cancer cell DNA repair mechanism, resulting in genomic dysfunction and cell death. In this study, we report the synthesis of a novel series of pyrano[2,3-d]pyrimidine-2,4-dione analogues as potential inhibitors against PARP-1. All the newly synthesized compounds were evaluated for their inhibitory activity towards PARP-1 and examined for their anti-proliferative activity against MCF-7 and HCT116 human cancer cell lines. The synthesized compounds showed promising activity where compounds S2 and S7 emerged as the most potent PARP-1 inhibitors with an IC₅₀ value of 4.06 ± 0.18 and

SUBMITTER: Abd El-Sattar NEA 

PROVIDER: S-EPMC8694318 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature