Potent and selective MAO-B inhibitory activity: Amino- versus nitro-3-arylcoumarin derivatives

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:25

Article

Joao Matos, Maria¹  Rodriguez-Enriquez, Fernanda²  Vilar, Santiago^1,3  Santana, Lourdes¹  Uriarte, Eugenio¹  Hripcsak, George³  Estrada, Martin⁴  Isabel Rodriguez-Franco, Maria⁴  Vina, Dolores² 

[1] Univ Santiago de Compostela, Fac Farm, Dept Quim Organ, Santiago De Compostela 15782, Spain

[2] Univ Santiago de Compostela, CIMUS, Dept Farmacol, Santiago De Compostela 15782, Spain

[3] Columbia Univ, Med Ctr, Dept Biomed Informat, New York, NY 10032 USA

[4] IQM CSIC, Inst Quim Med, Madrid 28006, Spain

关键词: 3-Arylcoumarins;    Perkin reaction;    Monoamine oxidase inhibitors;    PAMPA assay;    ADME theoretical properties;    Docking studies;   

DOI  :  10.1016/j.bmcl.2014.12.001

来源: Elsevier

【 摘 要 】

In this study we synthesized and evaluated a new series of amino and nitro 3-arylcoumarins as hMAO-A and hMAO-B inhibitors. Compounds 2, 3, 5 and 6 presented a better activity and selectivity profile against the hMAO-B isoform (IC50 values between 2 and 6 nM) than selegiline. In general, the amino derivatives (4-6) proved to be more selective against MAO-B than the nitro derivatives (1-3). Additionally, a theoretical study of some physicochemical properties, PAMPA and reversibility assays for the most potent derivative, and molecular docking simulations were carried out to further explain the pharmacological results, and to identify the hypothetical binding mode for the compounds inside the hMAO-B. (C) 2014 Elsevier Ltd. All rights reserved.

【 授权许可】

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