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

Area of Science:

• Medicinal Chemistry
• Microbiology
• Drug Discovery

Background:

• Biotin is essential for Mycobacterium tuberculosis survival.
• 7,8-Diamino pelargonic acid aminotransaminase (DAPA) is a key enzyme in biotin biosynthesis.
• Targeting biotin biosynthesis presents a potential strategy against tuberculosis.

Purpose of the Study:

• To synthesize and evaluate novel benzothiazole compounds for anti-tubercular activity.
• To identify compounds effective against both drug-susceptible and multidrug-resistant M. tuberculosis strains.
• To investigate the binding affinity and mode of action using molecular docking.

Main Methods:

• Synthesis of benzothiazole derivatives.
• In vitro anti-tubercular activity testing using the agar incorporation method against H37Rv and MDR-MTB strains.
• Molecular docking studies to predict binding affinity and interactions.

Main Results:

• One synthesized benzothiazole compound exhibited significant in vitro activity.
• Minimum inhibitory concentrations (MICs) of 1 μg/mL against H37Rv and 2 μg/mL against MDR-MTB were recorded.
• The most active compound displayed the highest binding affinity (-24.75 kcal/mol) in molecular docking simulations.

Conclusions:

• The synthesized benzothiazole compound {2-(benzo[d]thiazol-2-yl-methoxy)-5-fluorophenyl}-(4-chlorophenyl)-methanone shows promising anti-tubercular properties.
• This compound is effective against both susceptible and multidrug-resistant M. tuberculosis.
• The study highlights the potential of targeting DAPA for novel anti-TB drug development.