Exploration of 2-benzylbenzimidazole scaffold as novel inhibitor of NF-κB

被引：24

作者：

Boggu, PullaReddy ^{[1
,2
]}

Venkateswararao, Eeda ^{[1
,2
]}

Manickam, Manoj ^{[1
,2
]}

Kwak, Dajin ^{[3
]}

Kim, Youngsoo ^{[3
]}

Jung, Sang-Hun ^{[1
,2
]}

机构：

[1] Chungnam Natl Univ, Coll Pharm, Taejon 305764, South Korea

[2] Chungnam Natl Univ, Inst Drug Res & Dev, Taejon 305764, South Korea

[3] Chungbuk Natl Univ, Coll Pharm, Cheongju 361763, South Korea

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2016年 / 24卷 / 08期

基金：

新加坡国家研究基金会;

关键词：

2-Benzylbenzimidazole; NF-kappa B inhibition; Inflammation; INACTIVATION; ACTIVATION; TRANSCRIPTION; CONDENSATION; CHALCONE; TARGET;

D O I：

10.1016/j.bmc.2016.03.012

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：

For finding the novel inhibitor of nuclear factor kappa B activity, a series of benzimidazole derivatives were rationally designed, synthesized and systematically studied for their in vitro activities against LPS induced NF-kappa B inhibition in RAW 264.7 cells using the SEAP assay based on the flexible chalcone JSH ((E)-1-(2-hydroxy-6-(isopentyloxy)phenyl)-3-(4-hydroxyphenyl)prop-2-en-1-one) which was previously reported. Although most of the benzimidazole derivatives showed strong inhibitory activity in low micromolar potency, 2-(4-methoxybenzyl)-1H-benzo[d]imidazole (3m; IC50 = 1.7 mu M) and 2-(2-meth oxybenzyl)-1H-benzo[d]imidazole (3n; IC50 = 2.4 mu M) showed the best inhibition. The structure activity relationship revealed that 2-benzylbenzimidazole scaffold with hydrogen bonding acceptor on phenyl ring appears as a pharmacophore. (C) 2016 Elsevier Ltd. All rights reserved.

引用

页码：1872 / 1878

页数：7

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