Synthesis and evaluation of novel 1,2,3-triazole-based acetylcholinesterase inhibitors with neuroprotective activity

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• 作者：Jia-Cheng Li^a ; ^&dagger ; ; Juan Zhang^b ; ^&dagger ; ; Mosar Corrê ; a Rodrigues^b ; De-Jun Ding^c ; Joã ; o Paulo Figueiró ; Longo^b ; Ricardo Bentes Azevedo^b ; Luis Alexandre Muehlmann^b ; ^d ; Cheng-Shi Jiang^a ; ^{jiangchengshi-20@163.com" class="auth_mail" title="E-mail the corresponding author}
• 关键词：1 ; 2 ; 3-Triazole ; Acetylcholinesterase ; Amyloid-β-peptide ; Neuroprotective ; Alzheimer&rsquo ; s disease
• 刊名：Bioorganic & Medicinal Chemistry Letters
• 出版年：2016
• 出版时间：15 August 2016
• 年：2016
• 卷：26
• 期：16
• 页码：3881-3885
• 全文大小：745 K

文摘

A series of new 1,2,3-triazole derivatives were synthesized and evaluated for anticholinesterase and neuroprotective activities. Some synthetic derivatives, especially compound 32, exhibited improved acetylcholinesterase (AChE) inhibitory activity by comparison with the hit 1, high selectivity toward AChE over butyrylcholinesterase (BuChE), and suitable in vitro neuroprotective effect against amyloid-β_25–35 (Aβ_25–35)-induced neurotoxicity in SH-SY5Y cells. Furthermore, these molecules have desired physicochemical properties in the range of CNS drugs and showed no cytotoxicity against two normal cells, including human keratinocytes HaCaT and murine fibroblasts NIH-3T3. The preliminary bioassay results and docking study indicated that compound 32 might be a promising lead compound with dual action for the treatment of Alzheimer’s disease.