Synthesis, Characterisation and Antifungal Evaluation of Some Novel Pyrazoline linked 1,2,4-Triazole Derivatives

The dramatic increase in invasive fungal infections as well as increasingly complex multi-drug resistant fungal strains has intensified the urgent need for discovery and characterization of new antifungal agents. In this study, we have synthesized several novel pyrazoline-1,2,4-triazole hybrid compounds utilizing three different synthetic routes for each compound through (a) Claisen-Schmidt condensation to form the pyrazolines; (b) use of hydrazine to prepare the pyrazoline ring; (c) use of an etherification approach to convert a triazole-thiol based 2,4-difluorobenzylidene intermediate into a 1,2,4-triazolepyrazoline hybrid. All synthetic intermediates were fully characterized by FT-IR, 1H NMR, and Mass spectroscopy to confirm their structures. The in-vitro antifungal activities of the compounds were assessed against clinical isolates of important fungal pathogens such as Aspergillus niger, Candida albicans, Candida glabrata and Candida tropicalis. Inhibition zones created by the compounds via the disc diffusion method were created based on the inhibition zones created by amphotericin B. Many pyrazoline-triazole hybrid compounds produced inhibition zones that were considerably greater than those produced by amphotericin B, particularly those with halogen substituents at C-5 of the aryl pyrazoline rings. Furthermore, the structure-activity relationships indicate that all halogen substituents (especially para fluoro and dichloro) were critical contributors to the antifungal activities exhibited by this group of compounds.