文献类型：期刊文献

英文题名：Development of Novel N-hydroxypyridone Derivatives as Potential Anti-Ischemic Stroke Agents

作者：Hu, Linghao[1,2];Feng, Hongxuan[3,4];Zhang, Hongguang[3];Yu, Songda[5];Zhao, Qinyuan[3,4];Wang, Wei[3];Bao, Fengxia[3];Ding, Xun[3,4];Hu, Jiajing[2];Wang, Manjiong[1,2];Xu, Yixiang[1,2];Wu, Zengrui[2];Li, Xiaokang[1,2];Tang, Yun[2];Mao, Fei[1,2];Chen, Xiaoyan[5];Zhang, Haiyan[3,4];Li, Jian[1,2]

机构：[1]East China Univ Sci & Technol, Sch Pharm, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China;[2]East China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab New Drug Design, Shanghai 200237, Peoples R China;[3]Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Shanghai 201203, Peoples R China;[4]Univ Chinese Acad Sci, Beijing 100049, Peoples R China;[5]Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China

年份：2020

卷号：63

期号：3

起止页码：1051

外文期刊名：JOURNAL OF MEDICINAL CHEMISTRY

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000514221700011)】；

基金：This work was supported by the National Natural Science Foundation of China (grants 81872747, 21672064, 81872859, and 81661148046), the National Key R&D Program of China (2017YFB0202600), the Innovative Research Team of High-level Local Universities in Shanghai, the National Special Fund for State Key Laboratory of Bioreactor Engineering (2060204), and the Shanghai Sailing Program (17YF1403600).

语种：英文

摘要：Our previous study had identified ciclopirox (CPX) as a promising lead compound for treatment of ischemic stroke. To find better neuroprotective agents, a series of N-hydroxypyridone derivatives based on CPX were designed, synthesized, and evaluated in this study. Among these derivatives, compound 11 exhibits significant neuroprotection against oxygen glucose deprivation and oxidative stress -induced injuries in neuronal cells. Moreover, compound 11 possesses good blood-brain barrier permeability and superior antioxidant capability. In addition, a complex of compound 11 with olamine-11.01a possesses good water solubility, negligible hERG inhibition, and superior metabolic stability. The in vivo experiment demonstrates that 11.01a significantly reduces brain infarction and alleviates neurological deficits in middle cerebral artery occlusion rats. Hence, compound 11.01a is identified in our research as a prospective prototype in the innovation of stroke treatment.