Investigations on the 2-thiazolylhydrazyne scaffold: Synthesis and molecular modeling of selective human monoamine oxidase inhibitors

被引：87

作者：

Chimenti, Franco ^{[1
]}

Bolasco, Adriana ^{[1
]}

Secci, Daniela ^{[1
]}

Chimenti, Paola ^{[1
]}

Granese, Arianna ^{[1
]}

Carradori, Simone ^{[1
]}

Yanez, Matilde ^{[2
,3
]}

Orallo, Francisco ^{[2
,3
]}

Ortuso, Francesco ^{[4
]}

Alcaro, Stefano ^{[4
]}

机构：

[1] Univ Roma La Sapienza, Dipartimento Chim & Tecnol Farm, I-00185 Rome, Italy

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

[3] Univ Santiago de Compostela, Inst Farm Ind, Fac Farm, E-15782 Santiago De Compostela, La Coruna, Spain

[4] Univ Catanzaro Magna Graecia, Dipartimento Sci Farmacobiol, I-88021 Roccelletta Di Borgia, CZ, Italy

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2010年 / 18卷 / 15期

关键词：

hMAO inhibitors; 2-Thiazolylhydrazyne; Molecular modeling; BIOLOGICAL EVALUATION; THIAZOLE DERIVATIVES; MAO;

D O I：

10.1016/j.bmc.2010.06.007

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

A new series of [4-(3-methoxyphenyl)-thiazol-2-yl]hydrazyne derivatives were synthesized in good yield (71-99%) and characterized by elemental analysis and H-1 NMR studies. The compounds were assayed for their in vitro human monoamine oxidase (hMAO) inhibitory activity and selectivity and most of them showed IC50 values in the nanomolar range, thus demonstrating our interest in this privileged scaffold. The most active and selective derivative (20), bearing a pyridine moiety on the C=N, displayed IC50 = 3.81 +/- 0.12 nM and selectivity ratio = 119 toward hMAO-B. Molecular modeling studies were carried out on recent and high resolution hMAO-A and hMAO-B crystallographic structures to better justify the enzyme-inhibitor interaction toward hMAO isoforms and to explain the structure-activity relationship of this kind of inhibitors. (C) 2010 Elsevier Ltd. All rights reserved.

引用

页码：5715 / 5723

页数：9

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