Design Synthesis And Evaluation Of Modified Triazoles For The Antimicrobial Activity

Abstract

In present research work, the a novel 1,2,4-triazole-pyridine hybrid derivatives were synthesized by simple and efficient method as given in Scheme I. A series of merged pharmacophore contaning1,2,4-triazoles and substituted benzyl groups via thio linkage was 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 pyridine linked 1,2,4-triazole-3-thiol (II). This was finally reacted with different substituted benzyl halides to produce 1,2,4-triazoles linked with substituted benzyl groups through thio linkage (III). Purity of the derivatives was confirmed by thin layer chromatography, combustion analysis and melting point. Structure of these derivatives was set up by determining 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 i.e. 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. newlineAll the synthesized derivatives were also evaluated for their analgesic and anti- inflammatory activities in mice and rats respectively. In animal studies, the derivative 3- (5-(4-nitrobenzylthio)-4H-1,2,4-triazol-3-yl)pyridine showed more potent analgesic activity and the derivative 3-(5-(2,4-dimethylbenzylthio)-4H-1,2,4-triazol-3-yl)pyridine showed more potent anti-inflammatory activity as compared to other derivatives. The results of the present study indicate that