Study On The Synthetic Method And Antifungal Activity Of Triazole Analogues

Up to now, the multifunctional triazoles have found numerous applications in organic synthesis, as well as in medicine and industry. Our research concentrated on both 1,2,3-triazoles and 1,2,4-triazoles.More interest has been directed in the last few years to the chemistry and biological activities of 1,2,3-triazoles. Unfortunately, no good method for the preparation of 1,2,3-triazoles is readily available. The only method for the synthesis of 2,4-diaryl-1,2,3-triazoles was the intramolecular condensation of bisarylhydrazones. In order to provide more 1,2,3-triazole and its derivatives for their biological studies, it is necessary to develop a simple and cost effective synthesis route for the synthesis of 1,2,3-triazoles.As a part of our ongoing program aimed at searching for novel synthesis route for 1,2,3-triazoles, we found an efficient method to obtain a series of 1,2,3-triazole by cyclization between a -aminoacetophenone and hydrazine derivatives. This method is better than those disclosed in prior art due to the availability of the starting materials and the simple one-pot operation. Various a-aminoacetophenones bearing substituents on benzene ring were reacted with hydrazine derivatives to evaluate the scope of this new method. Sixteen 2,4-disubstituted-1,2,3-triazoles were obtained with this new method with moderate to good yields.The nucleus of 1,2,4-triazole were believed to inhibit the bio-synthesis of ergosterol in fungi which is the main constituent of fungal cell membrane. While these classes of compounds have been frequently used in the treatment of fungal infections, resistance to these drugs has also been rising, therefore indicating an urgent need for newer types of antiftmgal agents.Prompted by biological properties of 1,2,4-triazoles, we have recently disclosed 2-aryl-l,2,4-triazolo [1,5-a] pyridine as a novel structure class of triazole-based antifungal agents. This new class of compounds was synthesized by 1,3-dipolar cycloaddition of substituted N-aminopyridinium mesitylenesulfonate with aromatic nitriles in the presence of potassium hydroxide solution. Thirteen compounds (LOl-13) were synthesized. All of them have not been reported yet.The thirteen 2-aryl-l,2,4-triazolo [1,5-a] pyridine compounds were tested in vitro for their growth inhibitory activities against pathogenic fungi using the standard method. The MIC values indicate that the activities of three compounds were superior or comparable to fluconazole against both tested fungi. The results of this study suggest that 2-aryl-l,2,4-triazolo [1,5-a] pyridines could be a new class of 1,2,4-trizloe antifungal agents, worthy of further investigation of its antifungal activities.