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

作者：Samala Ganesh; Devi Parthiban Brindha; Saxena Shalini; Meda Nikhila; Yogeeswari Perumal; Sriram Dharmarajan^*

来源：Bioorganic & Medicinal Chemistry, 2016, 24(6): 1298-1307.

DOI：10.1016/j.bmc.2016.01.059

• Tuberculosis
• Pantothenate synthetase
• Imidazo[2,1-b]thiazole
• Benzo[d]imidazo[2,1-b]thiazole

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.

• 出版日期2016-3-15