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.
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Abstract | :
In the present study, we have designed imidazo[2,1-b]thiazole and benzo[d]imidazo[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-phenoxybenzoyl)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 μM, MIC of 3.53 μM, 2.1 log reduction against nutrient starved MTB, with 33% cytotoxicity at 50 μM. It also showed 1.5 log reduction of M. marinum load in Zebra fish at 10mg/kg. |
Year of Publication | :
2016
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Journal | :
Bioorganic & medicinal chemistry
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Volume | :
24
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Issue | :
6
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Number of Pages | :
1298-307
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Date Published | :
2016
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ISSN Number | :
0968-0896
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URL | :
https://linkinghub.elsevier.com/retrieve/pii/S0968-0896(16)30072-4
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DOI | :
10.1016/j.bmc.2016.01.059
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Short Title | :
Bioorg Med Chem
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