Synthesis and biological evaluation of fluconazole analogs with triazole-modified scaffold as potent antifungal agents.
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.
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.
Seyedeh Mahdieh
SM
Hashemi
Department of Medical Mycology & Parasitology/Invasive Fungi Research Center (IFRC), Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.
Hamid
H
Badali
Department of Medicinal Chemistry and Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran.
Hamid
H
Irannejad
Department of Toxicology and Pharmacology, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran.
Mohammad
M
Shokrzadeh
Department of Medicinal Chemistry and Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran. Electronic address: sd_emami@yahoo.com.
Saeed
S
Emami
D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D004353:Drug Evaluation, Preclinical / Q000379:methods; D015725:Fluconazole / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D056945:Hep G2 Cells; D006801:Humans; D008826:Microbial Sensitivity Tests; D014230:Triazoles / Q000138:chemical synthesis* / Q000494:pharmacology
D000935:Antifungal Agents; D014230:Triazoles; D015725:Fluconazole
Antifungal activity; Azole antifungals; Fluconazole; Lanosterol 14α-demethylase; Triazoles