In silico to in vitro screening of hydroxypyridinones as acetylcholinesterase inhibitors

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• 作者：Maria A. Telpoukhovskaia^&dagger ; ; Brian O. Patrick ; Cristina Rodrí ; guez-Rodrí ; guez ; ^{cristina.rodriguez@ubc.ca" class="auth_mail" title="E-mail the corresponding author} ; Chris Orvig ; ^{orvig@chem.ubc.ca" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Hydroxypyridinone ; Dimethylcarbamate ; Acetylcholinesterase ; Inhibitor ; Virtual library screening
• 刊名：Bioorganic & Medicinal Chemistry Letters
• 出版年：2016
• 出版时间：15 March 2016
• 年：2016
• 卷：26
• 期：6
• 页码：1624-1628
• 全文大小：937 K

文摘

We have previously shown the improved acetylcholinesterase inhibitory activity of a model hydroxypyridinone compound transforming the hydroxyl group on the main ring into an N,N-dimethylcarbamate group; in the course of that study we developed a computational model to screen compounds for enzymatic activity. Herein we report development of second generation libraries. Candidates that adhere to drug-like criteria from a virtual library of compounds were tested using computational docking studies. Synthesis and characterization of chosen test compounds and their acetylcholinesterase inhibitory activity are presented.