Triazolo-pyridine derivatives: Synthesis, characterization and biological evaluation

Abstract

A novel series of 8-chloro-3-phenyl-[1,2,4]triazolo[4,3-a]pyridine derivatives (4a-4j) were synthesized via the reaction of 3-chloro-2-hydrazinopyridine (2) with substituted aldehydes (3a-3j). The compounds (4a-4j) were evaluated for antitubercular, antibacterial, and antioxidant activities. The derivatives 4g and 4h exhibited potent MIC values 5.2 ± 0.22 µg/mL and 3.25 ± 0.12 µg/mL respectively comparable to rifampicin. In addition, molecular docking studies were performed to investigate the binding interaction modes of the compounds (4a-4j) with active sites of Mycobacterium tuberculosis cytochrome P450 enzyme CYP121 (PDB ID: 4G2G). Structure activity relationship analysis revealed the critical role of hydrogen bonding and aromatic stacking interactions in CYP121 binding, with balanced lipophilicity (LogP 2.5-3.5) and moderate TPSA (30-50 Ų) emerging as key determinants of activity. These results highlight triazolo-pyridine scaffolds as promising leads for antitubercular, antibacterial and antioxidant drug development.