title: Novel triazole alcohol antifungals derived from fluconazole: design, synthesis, and biological activity.
abstract: A series of new triazole alcohol antifungals were designed by replacing one of the triazolyl moiety from fluconazole with a distinct 4-amino-3-mercapto-1,2,4-triazole motif, which is found in some antimicrobial agents. The antimicrobial susceptibility testing of target compounds demonstrated that the direct analogs of fluconazole (difluorophenethyl-triazoles) were less active against fungi, while compound 10h containing dichloro substitutions on both phenyl rings of the molecule had potent activity against yeasts including Candida albicans (four strains) and Cryptococcus neoformans (MICs = 2-8 μg/mL). Also, compound 10h was active against Candida parapsilosis, Epidermophyton floccosum, and Trichophyton mentagrophytes, while it showed no activity against Gram-positive and Gram-negative bacteria. Finally, a molecular docking study suggested that compound 10h interacts suitably with lanosterol 14α-demethylase, which is the key enzyme in ergosterol biosynthesis.
authors.affiliation: Student Research Committee, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran.
authors.forename: Seyedeh Mahdieh
authors.initials: SM
authors.lastname: Hashemi
authors.forename: Hamid
authors.initials: H
authors.lastname: Badali
authors.forename: Mohammad Ali
authors.initials: MA
authors.lastname: Faramarzi
authors.forename: Nasrin
authors.initials: N
authors.lastname: Samadi
authors.forename: Mohammad Hosein
authors.initials: MH
authors.lastname: Afsarian
authors.forename: Hamid
authors.initials: H
authors.lastname: Irannejad
authors.forename: Saeed
authors.initials: S
authors.lastname: Emami
mesh_terms: D000935:Antifungal Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D060326:Chemistry Techniques, Synthetic; D015725:Fluconazole / Q000031:analogs & derivatives* / Q000737:chemistry; D005658:Fungi / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D013237:Stereoisomerism; D014230:Triazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D000935:Antifungal Agents; D014230:Triazoles; D015725:Fluconazole