Abstract

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

Teli Rahul V., Suprita N. Vibhutihalli, Samiksha A. Aitawade, Suprita M. Awati, Pavitra Nidagundi, *Somashekhar M. Metri

Abstract

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, 1HNMR, 13C-NMR, and mass spectroscopy. In-silico druglikeness, 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- www.wjpr.net │ Vol 15, Issue 18, 2026. │ ISO 9001: 2015 Certified Journal │ 660

Keywords: Pyrimidine, Isoniazid, Insilco study, ADME Analysis, Anti-TB activity.