Synthesis and biological evaluation of 3-substituted 5-benzylidene-1-methyl-2-thiohydantoins as potent NADPH oxidase (NOX) inhibitors

被引：21

作者：

Bae, Yun Soo ^{[1
]}

Choi, Sun ^{[2
,3
]}

Park, Jung Jae ^{[4
,5
]}

Joo, Jung Hee ^{[1
]}

Cui, Minghua ^{[2
,3
]}

Cho, Hyunsung ^{[4
,5
]}

Lee, Won Jae ^{[6
]}

Lee, Sang Hyup ^{[4
,5
]}

机构：

[1] Ewha Womans Univ, Coll Nat Sci, Dept Life Sci, Seoul 03760, South Korea

[2] Ewha Womans Univ, Coll Pharm, Seoul 03760, South Korea

[3] Ewha Womans Univ, Grad Sch Pharmaceut Sci, Seoul 03760, South Korea

[4] Duksung Womens Univ, Coll Pharm, Seoul 01369, South Korea

[5] Duksung Womens Univ, Innovat Drug Ctr, Seoul 01369, South Korea

[6] Seoul Natl Univ, Dept Life Sci, Seoul 08826, South Korea

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2016年 / 24卷 / 18期

基金：

新加坡国家研究基金会;

关键词：

Thiohydantoin; Benzylidene; Aluminum chloride; NADPH oxidase (NOX); EXPRESSION;

D O I：

10.1016/j.bmc.2016.06.056

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：

We report the synthesis of novel 3-substituted 5-benzylidene-1-methyl-2-thiohydantoins 3, and their biological evaluation using NADPH oxidase (NOX) 1 and 4. Based on structural and pharmacophore analyses of known inhibitors such as hydroxypyrazole 2, we envisioned interesting 2-thiohydantoin compounds, 3-substituted 5-benzylidene-1-methyl-2-thiohydantoins 3 that would be expected to well match the structural features in 2. Efficient synthesis of eighteen target compounds 3 were achieved through the synthetic pathway of 4 -> 11 -> 3, established after consideration of several plausible synthetic pathways. The inhibitory activities of compounds 3 against NOX 1 and 4 were measured, with some of the target compounds showing similar or higher activities compared with reference 2; in particular, compounds 3bz, 3cz, and 3ez were found to be promising inhibitors of both NOX 1 and 4 with modest isozyme selectivities, which highlights the significance of the 2-thiohydantoin substructure for inhibition of NOX 1 and 4. This marks the first time these compounds have been applied to the inhibition of NOX enzymes. (C) 2016 Elsevier Ltd. All rights reserved.

引用

页码：4144 / 4151

页数：8

共 32 条

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