Design, Synthesis and Activity Evaluation of New Phthalazinone PARP Inhibitors

نویسندگان

چکیده

Poly(ADP-ribose)polymerase (PARP) is a significant therapeutic target for the treatment of numerous human diseases. Olaparib has been approved as PARP inhibitor. In this paper, series new compounds were designed and synthesized with lead compound. order to evaluate inhibitory activities against PARP1 compounds, in vitro inhibition assay intracellular PARylation conducted. The results showed that derivatives related type substituent length alkyl chain connecting aromatic ring. 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT)-based also proved these demonstrating strong have high anti-proliferative BRCA2-deficient cell line (Capan-1). Analysis entire suggest compound 23 desirable efficiency may hold promise further vivo exploration inhibition.

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ژورنال

عنوان ژورنال: Chemical & Pharmaceutical Bulletin

سال: 2021

ISSN: ['0009-2363', '1347-5223']

DOI: https://doi.org/10.1248/cpb.c20-01018