Synthesis and Study of a Series of 3-Arylcoumarins as Potent and Selective Monoamine Oxidase B Inhibitors

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• 作者：Maria J. Matos ; Carmen Ter谩n ; Yunierkis P茅rez-Castillo ; Eugenio Uriarte ; Lourdes Santana ; Dolores Vi帽a
• 刊名：Journal of Medicinal Chemistry
• 出版年：2011
• 出版时间：October 27, 2011
• 年：2011
• 卷：54
• 期：20
• 页码：7127-7137
• 全文大小：985K
• 年卷期：v.54,no.20(October 27, 2011)
• ISSN：1520-4804

文摘

New series of 6-substituted-3-arylcoumarins displaying several alkyl, hydroxyl, halogen, and alkoxy groups in the two benzene rings have been designed, synthesized, and evaluated in vitro as human monoamine oxidase A and B (hMAO-A and hMAO-B) inhibitors. Most of the studied compounds showed a high affinity and selectivity to the hMAO-B isoenzyme, with IC₅₀ values on nanomolar and picomolar range. Ten of the 22 described compounds displayed higher MAO-B inhibitory activity and selectivity than selegiline. Coumarin 7 is the most active compound of this series, being 64 times more active than selegiline and also showing the highest hMAO-B specificity. In addition, docking experiments were carried out on hMAO-A and h-MAO-B structures. This study provided new information about the enzyme鈥搃nhibitor interaction and the potential therapeutic application of this 3-arylcoumarin scaffold.