(E)-3-Heteroarylidenechroman-4-ones as potent and selective monoamine oxidase-B inhibitors

被引：32

作者：

Desideri, Nicoletta ^{[1
]}

Monaco, Luca Proietti ^{[1
]}

Fioravanti, Rossella ^{[1
]}

Biava, Mariangela ^{[1
]}

Yanez, Matilde ^{[2
]}

Alcaro, Stefano ^{[3
]}

Ortuso, Francesco ^{[3
]}

机构：

[1] Univ Roma La Sapienza, Dipartimento Chim & Tecnol Farmaco, Ple Aldo Moro 5, I-00185 Rome, Italy

[2] Univ Santiago de Compostela, Fac Farm, Dept Farmacol, Campus Univ Sur, E-15782 Santiago De Compostela, La Coruna, Spain

[3] Magna Graecia Univ Catanzaro, Dipartimento Sci Salute, Campus Univ S Venuta,Viale Europa, I-88100 Catanzaro, Italy

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2016年 / 117卷

关键词：

Monoamine oxidases; Selective hMAO-B inhibitors; Chroman-4-ones; Homoisoflavonoids; Docking studies; EXOCYCLIC ALPHA; BETA-UNSATURATED KETONES; HOMOISOFLAVONOIDS; SCAFFOLD;

D O I：

10.1016/j.ejmech.2016.03.081

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of (E)-3-heteroarylidenechroman-4-ones (1a-r) was designed, synthesized and investigated in vitro for their ability to inhibit the enzymatic activity of both human monoamine oxidase (hMAO) isoforms, hMAO-A and hMAO-B. All the compounds were found to be selective hMAO-B inhibitors showing IC50 values in the nanomolar or micromolar range. (E)-5,7-Dichloro-3-{[(2-(dimethylamino) pyrimidin-5-yl]methylene}chroman-4-one (1c) was the most interesting compound identified in this study, endowed with higher hMAO-B potency (IC50 = 10.58 nM) and selectivity (SI > 9452) with respect to the reference selective inhibitor selegiline (IC50 = 19.60 nM, IC50 > 3431). Molecular modelling studies were performed for rationalizing at molecular level the target selective inhibition of our compounds, revealing a remarkable contribution of hydrogen bond network and water solvent. (C) 2016 Elsevier Masson SAS. All rights reserved.

引用

页码：292 / 300

页数：9

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