Tacrine鈥揊erulic Acid鈥揘itric Oxide (NO) Donor Trihybrids as Potent, Multifunctional Acetyl- and Butyrylcholinesterase Inhibitors

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• 作者：Yao Chen ; Jianfei Sun ; Lei Fang ; Mei Liu ; Sixun Peng ; Hong Liao ; Jochen Lehmann ; Yihua Zhang
• 刊名：Journal of Medicinal Chemistry
• 出版年：2012
• 出版时间：May 10, 2012
• 年：2012
• 卷：55
• 期：9
• 页码：4309-4321
• 全文大小：568K
• 年卷期：v.55,no.9(May 10, 2012)
• ISSN：1520-4804

文摘

In search of multifunctional cholinesterase inhibitors as potential anti-Alzheimer drug candidates, tacrine鈥揻erulic acid鈥揘O donor trihybrids were synthesized and tested for their cholinesterase inhibitory activities, release of nitric oxide, vasodilator properties, cognition improving potency, and hepatotoxicity. All of the novel target compounds show higher in vitro cholinesterase inhibitory activity than tacrine. Three selected compounds (3a, 3f, and 3k) produce moderate vasorelaxation in vitro, which correlates with the release of nitric oxide. Compared to its non-nitrate dihybrid analogue (3u), the trihybrid 3f exhibits better performance in improving the scopolamine-induced cognition impairment (mice) and, furthermore, less hepatotoxicity than tacrine.