Investigation of Potent Anti-<i>Mycobacterium tuberculosis</i> Agents Derived from Pyridine Derivatives Targeting the Enoyl Acyl Carrier Protein Reductase (InhA): Design, Synthesis, and Computational Analysis

Introduction Tuberculosis is a very complicated disease because of how the TB bacteria behaves in the human body. This makes it hard to diagnose, treat, and control. Because of this, the World Health Organization's latest reports show that there are still very few good treatment options for drug-resistant TB. Methods A novel series of pyridine-derived compounds were rationally designed and synthesized to evaluate their potential as antitubercular agents. These derivatives were specifically developed to target the enoyl acyl carrier protein reductase (InhA), and molecular docking studies were performed to predict binding modes with InhA. Results All compounds exhibited notable antitubercular activity, with minimum inhibitory concentrations (MIC) ranging from 0.5 to 2.0 μg mL -1 against Mycobacterium tuberculosis H37Rv. Discussion Derivative 6 was the most potent compound (MIC: 0.5 μg mL -1 ), inhibiting intracellular bacteria, disrupting biofilms, and potently targeting InhA (IC 5 0 : 0.36 μM). Its pyridine-thiazole scaffold was key for stable binding, as shown by molecular modeling.