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Novel triazole alcohol antifungals derived from fluconazole: design, synthesis, and biological activity

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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 \({\upmu }\)g/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 14\(\alpha \)-demethylase, which is the key enzyme in ergosterol biosynthesis.

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Acknowledgments

This work was supported by a grant from the Research Council of Mazandaran University of Medical Sciences, Sari, Iran. This work was related to the Ph.D. thesis of SMH (Faculty of Pharmacy, Mazandaran University of Medical Sciences).

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Author notes

  1. Mohammad Hosein Afsarian

    Present address: Departments of Microbiology, Fasa University of Medical Sciences, Fasa, Iran

Authors and Affiliations

  1. Student Research Committee, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran

    Seyedeh Mahdieh Hashemi

  2. Department of Medical Mycology & Parasitology/Invasive Fungi Research Center (IFRC), Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran

    Hamid Badali & Mohammad Hosein Afsarian

  3. Department of Pharmaceutical Biotechnology, Faculty of Pharmacy and Biotechnology Research Center, Tehran University of Medical Sciences, Tehran, Iran

    Mohammad Ali Faramarzi

  4. Department of Drug and Food Control, Faculty of Pharmacy and Pharmaceutical Quality Assurance Research Center, Tehran University of Medical Sciences, Tehran, Iran

    Nasrin Samadi

  5. Department of Medicinal Chemistry and Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran

    Hamid Irannejad & Saeed Emami

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  1. Seyedeh Mahdieh Hashemi
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Correspondence to Saeed Emami.

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Hashemi, S.M., Badali, H., Faramarzi, M.A. et al. Novel triazole alcohol antifungals derived from fluconazole: design, synthesis, and biological activity. Mol Divers 19, 15–27 (2015). https://doi.org/10.1007/s11030-014-9548-0

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  • DOI: https://doi.org/10.1007/s11030-014-9548-0

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