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 μg/ml had better profile of activity in respect to fluconazole (MICs = 0.5-4 μg/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 μg/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. [Formula: see text].