Neuroprotective effects of mercaptoethylleonurine and mercaptoethylguanidine analogs on hydrogen peroxide-induced apoptosis in human neuronal SH-SY5Y cells |
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| Authors: | Zhao-Lin Que Wen-Jiang Zhou Jun Chang Xin-Hua Liu Jian-Ming Yu Xun Sun |
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| Institution: | 1. Department of Natural Products Chemistry, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, China;2. Animal Center, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, China;3. Department of Pharmacology, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, China;4. Key Lab of Smart Drug Delivery, Ministry of Education & PLA, Fudan University, 826 Zhangheng Road, Shanghai 201203, China |
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| 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. |
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