Discovery of benzylthio analogs of fluconazole as potent antifungal agents

Aim: A new series of triazole alcohol antifungals 8a-j were designed by introducing benzylthio functionality on one triazole ring of fluconazole. Results: The antifungal activity evaluation of target compounds against 16 Candida isolates indicated that all compounds with MIC values of 0.063-1 mu g/ml had better profile of activity in respect to fluconazole (MICs = 0.5-4 mu g/ml) against fluconazole-susceptible isolates. In particular, the representative compounds 8b and 8e were also active against fluconazole-resistant isolates of Candida albicans and Candida parapsilosis (MICs = 0.063-16 mu g/ml). Cytotoxicity assay against Hep-G2 and NIH-3T3 cell lines revealed that these compounds can display potent antifungal activity at noncytotoxic concentrations. Conclusion: The prototype compound 8b could be considered as a new lead for design and development of potent antifungal agents. [GRAPHICS] .