Synthesis And Study On Antibacterial Activities Of3-(1H-1,2,4-triazole-1-yl)-Methylene-4-(N-substituted Phenyl)Imino-1,2,4-triazole-5-thiones

The1,2,4-triazole, a heterocyclic derivative is associated with a particularly strong biological property, such as antimicrobial activity, antifungal, antiviral, anticancer, anti-tubercular, etc. Bis-1,2,4-triazole derivatives containing more active sites exhibit overwhelming advantages in antimicrobial field. In this article, according to the biological activity of the principle of superposition, heterocyclic containing1,2,4-triazole with Schiff base prepared by substituted phenyl was reasonable assembled, we designed and synthesized3-(1H-1,2,4-triazole-l-yl)-methylene-4-(N-substituted phenyl)imino-1,2,4-triazole-5-thiones (A1-A8) and3-(1H-1,2,4-triazole-l-yl)-methylene-4-(N-substituted phenyl)amino-1,2,4-triazole-5-thiones (B1-B8).At first, Single ring1,2,4-triazole derivatives was synthesized by formamide and hydrazine hydrate. Then, by esterification, hydrazinolysis, salify, cycliztion and condensation reactions, bis-1,2,4-triazole Schiff base compounds3-(1H-1,2,4-triazole-l-yl)-methylene-4-(N-substituted phenyl)imino-1,2,4-triazole-5-thiones was synthesized. In the other series, Schiff base was reduced to3-(1H-1,2,4-triazole-l-yl)-methylene-4-(N-substituted phenyl) amino-1,2,4-triazole-5-thiones by sodium borohydride. The structures of all compounds have been confirmed by IR、1H NMR. All synthesized novel compounds were screened for their in vitro antibacterial activities.The in vitro antimicrobial activity data showed that all target compounds possessed efficient antibacterial activities against Staphylococcus aureus, Monilia albican, Bacillus subtilis and Escherichia coli. All target compounds showed excellent activity against Escherichia coli, which were more effective than the reference drug Fluconazole. Especially, the compound with two halogen atoms exhibited broad spectrum antimicrobial activity with minimum values of MIC to all the four strains. The compound with two halogen atoms showed excellent activity against Monilia albican and Bacillus subtilis, which were more effective than Triclosan and more effective than Fluconazole against Escherichia coli Staphylococcus aureus. Schiff base are better than that of the corresponding reduction structure against Staphylococcus aureus, Monilia albican, Bacillus subtilis.The structure activity relationship of the synthesized compounds showed that the presence of o-hydroxy in phenyl ring can significantly increase the inhibitory rate; and the presence of-Br、-Cl group in phenyl ring enhance the affinity for the compounds of the pathogen. The more halogen atoms the compounds have, the better antibacterial activity the compounds is. The structure of Schiff base play an important role in the antibacterial activity of the compounds, this conclusion coincidence in principle of reinforcement of biological activities.