title: Synthesis and biological evaluation of aryloxyacetamide derivatives as neuroprotective agents.
abstract: A series of new aryloxyacetamide derivatives 10a-s and 14a-m are designed and synthesized. Their protective activities against the glutamate-induced cell death were investigated in differentiated rat pheochromocytoma cells (PC12 cells). Most compounds exhibited neuroprotective effects, especially for 10m, 10r, 14b and 14c, which showed potential protection of PC12 cells at three doses (0.1, 1.0, 10μM). MTT assay, Hoechst 33342/PI double staining, and high content screening (HCS) revealed that pretreatment of the cells with 10m, 10r, 14b and 14c has significantly decreased the extent of cell apoptosis in a dose-dependent manner. The results of western blot analysis demonstrated these compounds suppressed apoptosis of glutamate-induced PC12 cells via caspase-3 pathway. These compounds can be lead compounds for further discovery of neuroprotective agents for treating cerebral ischemic stroke. Basic structure-activity relationships are also presented.
authors.affiliation: School of Chemistry and Chemical Engineering, Southeast University, Nanjing 211189, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhong
authors.affiliation: School of Pharmacy, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Xu
authors.affiliation: School of Pharmacy, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Ai-Xia
authors.initials: AX
authors.lastname: Zhang
authors.affiliation: School of Pharmacy, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Xiao-Feng
authors.initials: XF
authors.lastname: Li
authors.affiliation: School of Pharmacy, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Zhao-Ying
authors.initials: ZY
authors.lastname: Xu
authors.affiliation: School of Basic Medical Sciences, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.affiliation: School of Pharmacy, Nanjing Medical University, Nanjing 211166, China. Electronic address: wubin@njmu.edu.cn.
authors.forename: Bin
authors.initials: B
authors.lastname: Wu
mesh_terms: D000081:Acetamides / Q000737:chemistry; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D060326:Chemistry Techniques, Synthetic; D004353:Drug Evaluation, Preclinical / Q000379:methods; D018698:Glutamic Acid / Q000494:pharmacology; D057166:High-Throughput Screening Assays; D018696:Neuroprotective Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D016716:PC12 Cells; D051381:Rats; D013329:Structure-Activity Relationship
chemical_list: D000081:Acetamides; D018696:Neuroprotective Agents; D018698:Glutamic Acid; C030686:acetamide
keywords: Aryloxyacetamide; Caspase-3; Cerebral ischemic stroke; Neuroprotective activity