DESIGN, SYNTHESIS, CHARACTERIZATION AND DOCKING STUDY OF NOVEL PYRIDINE DERIVATIVES AS ANTITUBERCULAR ACTIVITY

The present study was undertaken to design, synthesize, characterize, and evaluate novel pyridine derivatives for their potential antitubercular activity. Pyridine-4-carbohydrazide was prepared from pyridine-4-carboxylic acid and subsequently used for the synthesis of novel derivatives, including PR4SII-A, PR4SII-B, and PR4SII-C. The synthesized compounds were characterized using spectroscopic techniques including IR, 1H-NMR, 13C-NMR, and mass spectroscopy. In-silico drug-likeness, ADMET, toxicity prediction, and molecular docking studies were performed to assess their pharmacokinetic properties, preliminary safety profile, and interaction with the antitubercular target dihydrofolate reductase (PDB ID: 1DF7). Among the synthesized compounds, PR4SII-B exhibited the most favorable docking score of −8.3 kcal/mol, showing interactions with ASP A:27, TRP A:6, SER A:49, PHE A:31, and ILE A:14. The antitubercular activity of PR4SII-A and PR4SII-B was evaluated against Mycobacterium tuberculosis H37Rv using the Microplate Alamar Blue Assay (MABA). Both compounds demonstrated concentration-dependent inhibition of mycobacterial growth. At 100 µg/mL, PR4SII-A showed 61.79% inhibition with an IC₅₀ of 73.74 µg/mL, whereas PR4SII-B showed 65.09% inhibition with an IC₅₀ of 67.24 µg/mL. Overall, PR4SII-B demonstrated comparatively better docking performance and in-vitro antitubercular activity than PR4SII-A, indicating that it may serve as a promising lead for further investigation as an antitubercular agent.