Design, synthesis and biological evaluation of imidazo[2,1-b]thiazole and benzo[d]imidazo[2,1-b]thiazole derivatives as Mycobacterium tuberculosis pantothenate synthetase inhibitors

被引：60

作者：

Samala, Ganesh ^{[1
]}

Devi, Parthiban Brindha ^{[1
]}

Saxena, Shalini ^{[1
]}

Meda, Nikhila ^{[1
]}

Yogeeswari, Perumal ^{[1
]}

Sriram, Dharmarajan ^{[1
]}

机构：

[1] Birla Inst Technol & Sci Pilani, Dept Pharm, Hyderabad Campus, Hyderabad 500078, Andhra Pradesh, India

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2016年 / 24卷 / 06期

关键词：

Tuberculosis; Pantothenate synthetase; Imidazo[2,1-b]thiazole; Benzo[d]imidazo[2,1-b]thiazole; MARINUM; MODEL;

D O I：

10.1016/j.bmc.2016.01.059

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：

In the present study, we have designed imidazo[2,1-b]thiazole and benzoldlimidazo[2,1-b]thiazole derivatives from earlier reported imidazo[1,2-a]pyridine based Mycobacterium tuberculosis (MTB) pantothenate synthetase (PS) inhibitors. We synthesized thirty compounds and they were evaluated for MTB PS inhibition study, in vitro anti -TB activities against replicative and non-replicative MTB, in vivo activity using Mycobacterium marinum infected Zebra fish and cytotoxicity against RAW 264.7 cell line. Among them compound 2-methyl -N' -(4-p henoxybenzoyl)benzo [d] imidazo [2,1 -b]thiazole-3-carbohydrazide (5bc) emerged as potent compound active against MTB PS with IC50 of 0.53 +/- 0.13 mu M, MIC of 3.53 mu M, 2.1 log reduction against nutrient starved MTB, with 33% cytotoxicity at 50 mu M. It also showed 1.5 log reduction of M. marinum load in Zebra fish at 10 mg/kg. (C) 2016 Elsevier Ltd. All rights reserved.

引用

页码：1298 / 1307

页数：10

共 20 条

[1]

[Anonymous], 2017, Global tuberculosis report

[2] Evaluation of a nutrient starvation model of Mycobacterium tuberculosis persistence by gene and protein expression profiling [J].