Benzothiazole analogs as potential anti-TB agents: computational input and molecular dynamics |
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| Authors: | Katharigatta N Venugopala Mohammed A Khedr Melendhran Pillay Susanta K Nayak Sandeep Chandrashekharappa Bandar E Aldhubiab |
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| Institution: | 1. Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University , Al-Ahsa, 31982, Kingdom of Saudi Arabia;2. Department of Biotechnology and Food Technology, Durban University of Technology , Durban, 4001, South Africa;3. Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Helwan University , Ein Helwan, Cairo, 11795, Egypt;4. Department of Microbiology, National Health Laboratory Services, KZN Academic Complex, Inkosi Albert Luthuli Central Hospital , Durban, 4001, South Africa;5. Department of Chemistry, Visvesvaraya National Institute of Technology , Nagpur, Maharashtra, 440010, India;6. Institute for Stem Cell Biology and Regenerative Medicine , NCBS, TIFR, GKVK, Bellary Road, Bangalore, 560 065, India;7. Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University , Al-Ahsa, 31982, Kingdom of Saudi Arabia |
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| Abstract: | Biotin is very important for the survival of Mycobacterium tuberculosis. 7,8-Diamino pelargonic acid aminotransaminase (DAPA) is a transaminase enzyme involved in the biosynthesis of biotin. The benzothiazole title compounds were investigated for their in vitro anti-tubercular activity against two tubercular strains: H37Rv (ATCC 25,177) and MDR-MTB (multidrug-resistant M. tuberculosis, resistant to isoniazid, rifampicin, and ethambutol) by an agar incorporation method. The possible binding mode and predicted affinity were computed using a molecular docking study. Among the synthesized compounds in the series, the title compound {2-(benzod]thiazol-2-yl-methoxy)-5-fluorophenyl}-(4-chlorophenyl)-methanone was found to exhibit significant activity with minimum inhibitory concentrations of 1 μg/mL and 2 μg/mL against H37Rv and MDR-MTB, respectively; this compound showed the highest binding affinity (–24.75 kcal/mol) as well. |
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| Keywords: | Benzothiazole H37Rv MDR-MTB minimum inhibitory concentration Mycobacterium tuberculosis single crystal X-ray studies |
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