Discovery of naphthacemycins as a novel class of PARP1 inhibitors
| Autor: | Mu Yunlong, Xinhua Lu, Xuexia Zhang, Gao Jian, Jingtong Zhu, Zhihui Zheng, Xu Yan, Shen Wenbin |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Naphthacenes
High-throughput screening Clinical Biochemistry Cancer therapy Pharmaceutical Science Poly(ADP-ribose) Polymerase Inhibitors 01 natural sciences Biochemistry chemistry.chemical_compound PARP1 Drug Discovery Humans Nuclear protein Molecular Biology 010405 organic chemistry Organic Chemistry DNA Damage Repair High-Throughput Screening Assays 0104 chemical sciences Molecular Docking Simulation 010404 medicinal & biomolecular chemistry chemistry Cell culture Molecular Medicine Function (biology) DNA |
| Zdroj: | Bioorganic & Medicinal Chemistry Letters. 29:1904-1908 |
| ISSN: | 0960-894X |
| DOI: | 10.1016/j.bmcl.2019.05.055 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect