2. Academic Validation
  3. Synthesis and biological evaluation of fluconazole analogs with triazole-modified scaffold as potent antifungal agents

Synthesis and biological evaluation of fluconazole analogs with triazole-modified scaffold as potent antifungal agents

  • Bioorg Med Chem. 2015 Apr 1;23(7):1481-91. doi: 10.1016/j.bmc.2015.02.011.
Seyedeh Mahdieh Hashemi 1,  Hamid Badali 2,  Hamid Irannejad 3,  Mohammad Shokrzadeh 4,  Saeed Emami 5
Affiliations

Affiliations

  • 1 Student Research Committee, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran; Department of Medicinal Chemistry and Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran.
  • 2 Department of Medical Mycology & Parasitology/Invasive Fungi Research Center (IFRC), Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.
  • 3 Department of Medicinal Chemistry and Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran.
  • 4 Department of Toxicology and Pharmacology, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran.
  • 5 Department of Medicinal Chemistry and Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran. Electronic address: [email protected].
PMID: 25740636 DOI: 10.1016/j.bmc.2015.02.011
Abstract

In order to find new azole antifungals, we have recently designed a series of triazole alcohols in which one of the 1,2,4-triazol-1-yl group in fluconazole structure has been replaced with 4-amino-5-aryl-3-mercapto-1,2,4-triazole motif. In this paper, we focused on the structural refinement of the primary lead, by removing the amino group from the structure to achieve 5-aryl-3-mercapto-1,2,4-triazole derivatives 10a-i and 11a-i. The in vitro Antifungal susceptibility testing of title compounds demonstrated that most compounds had potent inhibitory activity against Candida species. Among them, 5-(2,4-dichlorophenyl)triazole analogs 10h and 11h with MIC values of <0.01 to 0.5μg/mL were 4-256 times more potent than fluconazole against Candida species.

Keywords

Antifungal activity; Azole antifungals; Fluconazole; Lanosterol 14α-demethylase; Triazoles.

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