Synthesis And In Vitro Antifungal Activity Of Antifungal Triazoles

All these years, major developments in research into the azole class of antifungal agents have provided expanded options for the treatment of many superficial and systemic fungal infections, such as Fluconazole, Itranconazole and Voriconazole, which proved to be safe and effctive, are recommended as the first choice of the antifungal drugs for treating fungal infections. Nowadays, azole compounds are the most widely and deeply studied class of antifungal agents. However, resistance to the available drugs even the cross resistance is emerging followed by the increasing drug resistant strain and hepatotoxicity is existing in all azole antifungal agents. Accordingly, the discovery of antifungal agents that possess broad antifungal spectrum, high potent and low toxicity remains an important topic on antifungal agents research.Using Fluconazole as a lead compound, thirty 1-(1H-1,2,4-triazol-l-yl)-2-(2,4-difluorophenyl)-3-substituted-2-propanols were synthesized according to the structure-activity relationship of azole antifungal agents, which contain keeping the active structures of triazole, tertiary alcohol and difluorophenyl. 3-phenylpyridine and biphenyl were introduced to the 3-position side chain. The structures of the compounds were confirmed by ¹HNMR, IRand HR-MS.Preliminary antifungal activities in vitro of the compounds were examined by broth macrodilution test against Candida albicans, Cryptococcus neoformans, Candida tropicalis, Candida parapsilosis, Aspergillus fumigatus, Trichophyton rubrum, Microsporum gypseum and Fonsecaea compacta. Most of the compounds showed higher potent in vitro activity against Candida albicans, Candida parapsilosis and Candida tropicalis than Voriconazole or comparable to Voriconazole. Especially, compounds B₁, B₃-3, B₄, B₅, A₃-1 and A₄-1 are worth further study. The discussion of the structure-activity relationship of the compounds will lead us to the further study of antifungal agents which possess broad antifungal spectrum, high potent and low toxicity.