title: Synthetic phenylethanoid glycoside derivatives as potent neuroprotective agents.
abstract: Several phenylethanoid glycoside derivatives were designed and synthesized. Most of the synthetic compounds showed significant neuroprotective effects, including antioxidative and anti-apoptotic properties. Specifically, target compounds displayed potent effects against various toxicities such as H2O2 and 6-hydroxydopamine (6-OHDA) in PC12 cells. Among the synthetic derivatives, three compounds (5, 6, 8) exhibited much superior activities to the marketed drug Edaravone. The compounds were able to prevent the 6-OHDA-induced damage in PC12 cells in a dose-dependent manner. The anti-apoptotic effects could be observed via cell morphological changes. Moreover, the compounds significantly reduced the intracellular ROS increase resulting from 6-OHDA treatment. The preliminary structure-activity relationships were also explored. Compounds 5, 6, 8 may hold the potential as promising neuroprotective agents and new lead compounds for the treatment of neurodegenerative diseases or cerebral ischemia.
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Xue Yuan Road No. 38, Beijing 100191, China.
authors.forename: Ying-Guo
authors.initials: YG
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Xue Yuan Road No. 38, Beijing 100191, China.
authors.forename: Xiaxi
authors.initials: X
authors.lastname: Li
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Xue Yuan Road No. 38, Beijing 100191, China.
authors.forename: De-Cai
authors.initials: DC
authors.lastname: Xiong
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Xue Yuan Road No. 38, Beijing 100191, China.
authors.forename: Binhan
authors.initials: B
authors.lastname: Yu
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Xue Yuan Road No. 38, Beijing 100191, China. Electronic address: pxp123@bjmu.edu.cn.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Pu
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Xue Yuan Road No. 38, Beijing 100191, China; National Engineering Research Center for Carbohydrate Synthesis, Jiangxi Normal University, Nanchang 330022, Jiangxi, China. Electronic address: xinshan@bjmu.edu.cn.
authors.forename: Xin-Shan
authors.initials: XS
authors.lastname: Ye
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D060326:Chemistry Techniques, Synthetic; D015195:Drug Design; D016166:Free Radical Scavengers / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D006027:Glycosides / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D018696:Neuroprotective Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D016716:PC12 Cells; D010539:Permeability; D051381:Rats; D013329:Structure-Activity Relationship
chemical_list: D016166:Free Radical Scavengers; D006027:Glycosides; D018696:Neuroprotective Agents
keywords: Anti-apoptosis; Antioxidant; Neuroprotective agent; Phenylethanoid glycoside; Structure modification