Discovery of benzylthio analogs of fluconazole as potent antifungal agents. (23rd April 2018)

• Record Type: Journal Article
• Authors: Motahari, Kamran; Badali, Hamid; Hashemi, Seyedeh Mahdieh; Fakhim, Hamed; Mirzaei, Hassan; Vaezi, Afsane; Shokrzadeh, Mohammad; Emami, Saeed
• Is Part Of: Future medicinal chemistry. Volume 10:Number 9(2018)
• Page Start: 987
• Page End: 1002
• Publication Date: 2018-04-23
• Subjects: antifungal activity -- azole antifungals -- fluconazole -- lanosterol 14α-demethylase -- triazole; Pharmaceutical chemistry -- Periodicals; 615.19005
• DOI: 10.4155/fmc-2017-0295
• Languages: English
• ISSNs: 1756-8919

Abstract

Aim: A new series of triazole alcohol antifungals8a–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 compounds8b and8e 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 compound8b could be considered as a new lead for design and development of potent antifungal agents.