Benzothiazole analogs as potential anti-TB agents: computational input and molecular dynamics

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.

Keywords:

• Benzothiazole
• H37Rv
• MDR-MTB
• minimum inhibitory concentration
• Mycobacterium tuberculosis
• single crystal X-ray studies

Abbreviations:

• 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

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Corrigendum

Acknowledgments

The authors are grateful to Deanship of Scientific Research, King Faisal University, Kingdom of Saudi Arabia for the financial support under grant number 17122011 and encouragement.