Discovery of naphthacemycins as a novel class of PARP1 inhibitors. Issue 15 (1st August 2019)

• Record Type: Journal Article
• Authors: Shen, Wenbin; Lu, Xinhua; Zhu, Jingtong; Mu, Yunlong; Xu, Yan; Gao, Jian; Zhang, Xuexia; Zheng, Zhihui
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 29:Issue 15(2019)
• Page Start: 1904
• Page End: 1908
• Publication Date: 2019-08-01
• Subjects: PARP1 inhibitor -- High-throughput screening -- Molecular docking -- Naphthacemycins -- Microbial metabolites; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2019.05.055
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: Poly (ADP-ribose) polymerase-1 (PARP-1) is an abundant nuclear protein that plays important roles in a variety of nuclear processes, and it has been proved a prominent target in oncology for its key function in DNA damage repair. In this study, we discovered a series of naphthacemycins as a new class of PARP1 inhibitors from a microbial metabolites library via high-throughput screening. Compound I, one of this series of compounds, could reduce cellular poly (ADP-ribose) level, trap PARP1 on the damaged DNA and elevate the level of γ-H2AX, and showed the selective cytotoxicity against BRCA1-deficient cell line. Our study provided a potential scaffold for the development of new PARP1 inhibitors in cancer therapy.