Design, Synthesis, and Cytoprotective Effect of 2-Aminothiazole Analogues as Potent Poly(ADP-Ribose) Polymerase-1 Inhibitors

摘要：

A series of novel poly(ADP-ribose) polymerase-1 (PARP-1) inhibitors were designed within 2aminothiazole analogues (4-10) based on a constructed three-dimensional pharmacophore model. After synthesis, the inhibitory effect on PARP-1 activity and the cytoprotective action of these compounds were tested and evaluated. Among them, compounds 4-6 and 10 appeared to be potent PARP-1 inhibitors with IC50 values less than 1 μM, which had been perfectly predicted by pharmacophore model. These compounds proved to be highly potent against cell injury induced by H2O2 and oxygen-glucose deprivation (OGD) in PC12 cells. These novel 2-aminothiazole analogues are potentially applicable as neuroprotective agents for the treatment of neurological diseases.

作者: Wen-Ting Zhang Gang-Ying Chen Yi-Jing Zhu Jun Gu Jian-Guo Chen Jin-Lan Ruan Peng-Fei Wu Feng-Chao Jiang Li-Na Zhang Wei Fang Xiang-Long Chen Yue Wang Bao-Shuai Cao

作者单位: Department of Medicinal Chemistry, Tongji Medical College, Huazhong University of Science and Techno Department of Pharmacology, Tongji Medical College, Huazhong University of Science and Technology Department of Pharmacology, Tongji Medical College, Huazhong University of Science and Technology Th Department of Medicinal Chemistry, Tongji Medical College, Huazhong University of Science and Techno

会议类型: 国际会议

会议名称: The 5th International Conference of Molecular Simulations and Applied Informatics Technologies(第五届国际分子模拟与信息技术应用学术会议 ICMS&I)

会议地点: 武汉

会议语种:英文

页码: 806-813

在线出版日期: 2010-09-01（万方平台首次上网日期，不代表论文的发表时间）