Synthesis, Characterization, Molecular Modeling, and Biological Evaluation of 1,2,4-Triazole-pyridine Hybrids as Potential Antimicrobial Agents

A novel 1,2,4-triazole-pyridine hybrid derivatives were synthesized by the reaction of nicotinohydrazide with carbon disulfide to yield potassium-3-pyridyl-dithiocarbazate (I). This was further cyclized with ammonia solution to yield 5-mercapto-substituted 1,2,4-triazole-pyridine hybrid (II). This was finally reacted with different substituted benzyl derivatives to produce 1,2,4-triazole-pyridine hybrid derivatives (III). The purity of the derivatives was confirmed by thin-layer chromatography and melting point. Structure of these derivatives was set up by determining its infrared spectroscopy, nuclear magnetic resonance spectroscopy, and mass spectroscopy. Further, the synthesized derivatives were evaluated for their in vitro antimicrobial activity against the three Gram-negative bacteria (Escherichia coli, Pseudomonas aeruginosa, and Acinetbacter baumannii), three Gram-positive bacteria (Staphylococcus aureus, Streptococcus pyogenes, and Enterococcus faecalis), and two fungus (Aspergillus clavatus and Candida albicans). Minimal inhibitory concentration was also determined against same microorganism. Out of all synthesized derivatives, two derivatives, that is, 3-(5-(2-bromobenzylthio)-4H-1,2,4-triazol-3-yl)pyridine and 3-(5-(2,4-dibromobenzylthio)-4H-1,2,4-triazol-3-yl)pyridine showing more potent antibacterial activity. Docking studies were performed by using Argus lab, and all the derivatives exhibited good docking scores between -10.5369 and -11.8477 kcal/mol and were better as compared with standard drug methotrexate against a dihydrofolate reductase protein fragment from E. coli and Lactobacillus (4DFR). Among all compounds, 4h has shown the maximum docking score and found in agreement to in vitro antimicrobial studies.