Synthesis of Pyrrole‐Based Hydrazone Derivatives: In Vitro Antitubercular Assays and Molecular Docking Studies

ABSTRACT Tuberculosis (TB), a disease caused by Mycobacterium tuberculosis ( M. tuberculosis ), remains a leading cause of mortality around the globe. The emergence of drug‐resistant TB strains has led the researchers to search for new chemotherapeutic agents. In this study, we report the synthesis, molecular docking, and biological evaluation of N' ‐((2,5‐dimethyl‐1‐phenyl‐1 H ‐pyrrol‐3‐yl) methylene) benzohydrazide derivatives as potential antitubercular agents. The target compounds were synthesized through a Schiff base condensation reaction between 2,5‐dimethyl‐1‐phenyl‐1 H ‐pyrrole‐3‐carbaldehyde and different substituted benzohydrazides. The synthesized compounds were confirmed by FT‐IR, 1 H NMR, 13 CNMR and mass spectrometric analyses. To understand more about the binding interactions of these compounds, molecular docking studies were performed using the crystal structure of enoyl‐acyl carrier protein reductase (InhA), a key enzyme in the mycolic acid synthesis pathway of M. tuberculosis . The docking study showed that several derivatives demonstrated effective binding energies, with SR‐11 standing out as the most potent. It exhibited the strongest binding affinity toward the crystal structure of M. tuberculosis InhA protein, achieving a docking score of –10.1 kcal/mol. Compounds such as SR‐1, SR‐06, SR‐07, SR‐08, SR‐12, SR‐16 , and SR‐17 exhibited favorable docking scores, ranging from –8.1 to –8.9 kcal/mol. Further antimycobacterial activities of the synthesized compounds were evaluated in vitro against the M. tuberculosis H37Rv strain using the Microplate Alamar Blue Assay (MABA). Several compounds demonstrated moderate activity with MIC values ranging from 6.25 to 12.5 µg/mL. These findings suggest that pyrrole‐based benzohydrazide derivatives are the early‐stage scaffolds for further development as antitubercular agents.