Inhibition of monoamine oxidases by coumarin-3-acyl derivatives: biological activity and computational study

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• 作者：Chimenti ; Franco ; Secci ; Daniela ; Bolasco ; Adriana ; Chimenti ; Paola ; Granese ; Arianna ; Befani ; Olivia ; et. al.
• 关键词：MAO-inhibitors ; Coumarin
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2004
• 期刊代码：10_0960894x
• 类别：ch
• 出版时间：July 16, 2004
• 卷：14
• 期：14
• 页码：3697-3703
• 文件大小：344 K

摘要

A series of coumarin-3-acyl derivatives have been synthesized and investigated for the ability to inhibit selectively monoamine oxidases. The coumarin-3-carboxylic acids, 2a–e, proved to be reversible and selective inhibitors of the MAO-B isoform, displaying pIC₅₀ values of particular interest: 2a shows pIC₅₀ 7.76 and a selectivity index (pS.I.) 2.94 and 2b shows pIC₅₀ 7.72 and a pS.I. of 2.80. The coumarin-3-acyl chlorides 3a–e showed high pIC₅₀ values against both MAO-A and MAO-B isoforms, 3d being the highest against MAO-B with a pIC₅₀ value of 8.00. In order to rationalize the activity/selectivity results, molecular descriptors were generated. Further insight about enzyme–inhibitor interaction was obtained by docking experiments with the MAO-B isoform.