Benzothiazole analogs as potential anti-TB agents: computational input and molecular dynamics. Issue 7 (3rd May 2019)

• Record Type: Journal Article
• Authors: Venugopala, Katharigatta N.; Khedr, Mohammed A.; Pillay, Melendhran; Nayak, Susanta K.; Chandrashekharappa, Sandeep; Aldhubiab, Bandar E.; Harsha, Sree; Attimard, Mahesh; Odhav, Bharti
• Is Part Of: Journal of biomolecular structure & dynamics. Volume 37:Issue 7(2019)
• Page Start: 1830
• Page End: 1842
• Publication Date: 2019-05-03
• Subjects: Benzothiazole -- H37Rv -- MDR-MTB -- minimum inhibitory concentration -- Mycobacterium tuberculosis -- single crystal X-ray studies; MDR-MTB: multidrug-resistant strains of M. tuberculosis -- XDR-MTB: extensively drug-resistant M. tuberculosis -- SAM: S-adenosylmethionine -- DAPA: 7, 8-diamino pelargonic acid aminotransferase -- PLP: Pyridoxal phosphate -- MIC: minimum inhibitory concentration; Biomolecules -- Periodicals; Molecular structure -- Periodicals; Molecular Biology -- Periodicals; Biomechanics -- Periodicals; 572
• DOI: 10.1080/07391102.2018.1470035
• Languages: English
• ISSNs: 0739-1102

Abstract

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-(benzo[ d ]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.