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

被引：158

作者：

Matos, Maria J. ^{[1
]}

Teran, Carmen ^{[2
]}

Perez-Castillo, Yunierkis ^{[2
]}

Uriarte, Eugenio ^{[1
]}

Santana, Lourdes ^{[1
]}

Vina, Dolores ^{[3
]}

机构：

[1] Univ Santiago de Compostela, Dept Organ Chem, Fac Pharm, Santiago De Compostela 15782, Spain

[2] Univ Vigo, Dept Organ Chem, Fac Chem, Vigo 36310, Spain

[3] Univ Santiago de Compostela, Dept Pharmacol, Fac Pharm, Santiago De Compostela 15782, Spain

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2011年 / 54卷 / 20期

关键词：

MAO-B; COUMARIN DERIVATIVES; INSIGHTS; ANALOGS; DESIGN; MODEL; 3-PHENYLCOUMARINS; RESVERATROL; SAFINAMIDE; RESOLUTION;

D O I：

10.1021/jm200716y

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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 cuddase 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 inhibitor interaction and the potential therapeutic application of this 3-arylcoumarin scaffold.

引用

页码：7127 / 7137

页数：11

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