Inhibition Potential of Schiff Bases Against the Target Enzymes of Mycobacterium Tuberculosis Using Molecular Docking

Tuberculosis (TB) is a chronic infectious disease caused by Mycobacterium tuberculosis (MT), an acid-fast, gram-positive bacillus that poses a major global health threat. Despite the availability of first-line and second-line anti-TB drugs, TB remains one of the top causes of mortality from infectious diseases, particularly in low- and middle-income countries. The emergence of multi-drug-resistant (MDR) and extensively drug-resistant (XDR) strains has significantly reduced the efficacy of existing treatment regimens, highlighting the urgent need to discover and develop novel therapeutic agents with enhanced efficacy and safety profiles. Schiff bases, known for their diverse biological activities, including antibacterial, antifungal, and anticancer properties, have recently gained attention as promising pharmacophores in drug development. In this study, we evaluated a series of vanillin-derived Schiff base compounds (S1–S6) for their potential anti-tubercular activity through molecular docking studies. The selected compounds were screened against two critical enzymes essential for the survival and proliferation of Mycobacterium tuberculosis: DprE1 (decaprenyl phosphoryl-β-D-ribose 2′-epimerase), involved in cell wall biosynthesis, and DNA gyrase subunit A, crucial for DNA replication. Molecular docking was performed to assess the binding affinity, binding modes, and interaction profiles of these ligands with the target proteins. The results demonstrated that all compounds (S1–S6) exhibited strong and favorable binding interactions with the active sites of both enzymes. Notably, their docking scores and interaction energies were superior to those of currently used anti-TB drugs such as isoniazid, bedaquiline, pyrazinamide, and the standard reference ethambutol (S7). These findings suggest that the vanillin-based Schiff bases have significant inhibitory potential against Mycobacterium tuberculosis and could serve as promising lead compounds for future in vitro and in vivo studies aimed at developing new anti-TB therapies