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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| Institution: | 1. Bio-Organic Chemistry Division, Indian Institute of Integrative Medicine (CSIR), Jammu, 180001, India;2. Academy of Scientific and Innovative Research (AcSIR), New Delhi, 110025, India;3. Department of Pharmaceutical Chemistry, Indo-Soviet Friendship College of Pharmacy (ISFCP), Moga, 142002, India;4. Department of Chemistry, National Institute of Technology (NIT) Jalandhar, 144011, Punjab, India;1. Torrey Pines Institute for Molecular Studies, 11350 SW Village Parkway, Port St. Lucie, FL 34987, United States;2. Department of Cell Biology, Microbiology and Molecular Biology, University of South Florida, 4202 East Fowler Avenue, Tampa, FL 33620, United States;1. Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran;2. Department of Medicinal Chemistry and Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran;3. Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran 14176, Iran;4. Persian Medicine and Pharmacy Research Center, Tehran University of Medical Sciences, Tehran, Iran;5. Department of Medicinal Chemistry, Faculty of Pharmacy, Shahid Sadoughi University of Medical Sciences, Yazd, Iran;6. Neurobiomedical Research Center, School of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran;1. Department of Pharmacy, Birla Institute of Technology & Science-Pilani, Hyderabad Campus, Hyderabad 500078, India;2. Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL, USA |
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| Abstract: | In the present study, we have designed imidazo2,1-b]thiazole and benzod]imidazo2,1-b]thiazole derivatives from earlier reported imidazo1,2-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)benzod]imidazo2,1-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 10 mg/kg. |
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| Keywords: | Tuberculosis Pantothenate synthetase |
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