title: Neuroprotective effects of mercaptoethylleonurine and mercaptoethylguanidine analogs on hydrogen peroxide-induced apoptosis in human neuronal SH-SY5Y cells.
abstract: A series of mercaptoethylleonurine and mercaptoethylguanidine derivatives were designed and synthesized. Their neuroprotective effects toward H2O2-induced apoptosis were investigated in human SH-SY5Y cells. The results from these studies identified several potent compounds, with compound 8k emerging as the most effective. Further investigation demonstrated that 8k reduced H2O2-induced activation of mitochondrial apoptosis by inhibiting the expression of Bax and elevating the expression of Bcl-2. Moreover, the molecular mechanism underlying the observed neuroprotective effects of 8k was exerted via the Akt and JNK pathways. Compound 8k can be a lead compound for further discovery of neuroprotective medicine.
authors: Department of Natural Products Chemistry, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, China.
authors: Zhao-Lin
authors: ZL
authors: Que
authors: Wen-Jiang
authors: WJ
authors: Zhou
authors: Jun
authors: J
authors: Chang
authors: Xin-Hua
authors: XH
authors: Liu
authors: Jian-Ming
authors: JM
authors: Yu
authors: Xun
authors: X
authors: Sun
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D006146:Guanidines / Q000737:chemistry; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity*; D009447:Neuroblastoma / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D006146:Guanidines; D018696:Neuroprotective Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D006861:Hydrogen Peroxide; C100078:2-mercaptoethylguanidine