Novel tacrine-1,2,3-triazole hybrids: In vitro, in vivo biological evaluation and docking study of cholinesterase inhibitors

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• 作者：Zahra Najafi^a ; Mohammad Mahdavi^b ; Mina Saeedi^c ; ^d ; Elahe Karimpour-Razkenari^d ; Raymond Asatouri^e ; Fahimeh Vafadarnejad^a ; Farshad Homayouni Moghadam^f ; Mahnaz Khanavi^g ; Mohammad Sharifzadeh^h ; ^{msharifzadeh@tums.ac.ir} ; Tahmineh Akbarzadeh^a ; ^d ; ^{akbarzad@tums.ac.ir}
• 关键词：Alzheimer's disease ; Cholinesterase ; Docking study ; Dual binding ; Morris water maze ; Tacrine-1 ; 2 ; 3-triazole
• 刊名：European Journal of Medicinal Chemistry
• 出版年：2017
• 出版时间：5 January 2017
• 年：2017
• 卷：125
• 期：Complete
• 页码：1200-1212
• 全文大小：2230 K
• 卷排序：125

文摘

Novel tacrine-1,2,3-triazole hybrids were synthesized and evaluated for their AChEI and BChEI activities. Compounds 5l and 5j depicted the most potent anti-AChE and anti-BChE activity, respectively. Also, compound 5l showed moderate neuroprotective activity. Compounds 5a, 5b, 5j, 5l, 5m, and 5n were subjected to cytotoxic assay. They showed no significant cytotoxicity. Molecular modeling and kinetic studies showed that compounds 5l and 5j bound simultaneously to the peripheral anionic site (PAS) and catalytic sites (CS) of the AChE and BChE. Compound 5l improved memory deficit in rat induced by scopolamine.