Promising Antimycobacterial Agents: Salicylidenehydrazines

Tuberculosis (TB) remains a major global health challenge, underscoring the urgent need for new therapeutic options. In this study, a series of salicylidenehydrazine derivatives were synthesized and characterized using spectroscopic techniques. Their antimycobacterial activity was assessed against Mycobacterium tuberculosis H37Rv. Among the 35 synthesized compounds, nine demonstrated significant inhibitory activity, with MIC values ranging from 0.78 to 50 μM. These active molecules were further evaluated against clinical isoniazid-resistant (bearing inhA promoter and/or katG mutations) and multidrug-resistant (MDR) M. tuberculosis strains. A particularly potent compound derived from 2-bromo-4-nitrosalicylaldehyde exhibited an MIC of 0.78 μM against H37Rv and demonstrated low MIC values of 6.25, 1.56, and 1.56 μM against the inhA + , katG + , and MDR strains, respectively. Molecular docking studies were also conducted to investigate the interaction of active compounds with the target enzyme InhA. Overall, the results indicate that salicylidenehydrazine derivatives represent promising lead structures for the development of new anti-TB agents effective against both drug-sensitive and drug-resistant M. tuberculosis strains.