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Design, synthesis and biological evaluation of novel 1,2,3-triazolyl \(\upbeta \)-hydroxy alkyl/carbazole hybrid molecules

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Abstract

The design, synthesis and biological study of several novel 1,2,3-triazolyl \(\upbeta \)-hydroxy alkyl/carbazole hybrid molecules as a new type of antifungal agent has been described. In this synthesis, the N-alkylation reaction of carbazol-9-ide potassium salt with 3-bromoprop-1-yne afforded 9-(prop-2-ynyl)-9H-carbazole. The ‘Click’ Huisgen cycloaddition reaction of 9-(prop-2-ynyl)-9H-carbazole with diverse \(\upbeta \)-azido alcohols in the presence of copper-doped silica cuprous sulphate led to target molecules in excellent yields. The in vitro antifungal and antibacterial activities of title compounds were screened against various pathogenic fungal strains, Gram-positive and/or Gram-negative bacteria. In particular, 1-(4-((9H-carbazol-9-yl) methyl)-1H-1,2,3-triazol-1-yl)-3-butoxypropan-2-ol (10e) proved to have potent antifungal activity against all fungal tests compared with fluconazole and clotrimazole as studied reference drugs. Our molecular docking analysis revealed an appropriate fitting and a potential powerful interaction between compound 10e and an active site of the Mycobacterium P450DM enzyme. The strong hydrogen bondings between \(\upbeta \)-hydroxyl and ether groups in 10e were found to be the main factors that drive the molecule to fit in the active site of enzyme. The in silico pharmacokinetic studies were used for a better description of 10a–10n as potential lead antifungal agents for future investigations.

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Acknowledgments

The authors wish to thank Shiraz University of Technology research council for partial support of this work.

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Authors and Affiliations

  1. Department of Chemistry, Shiraz University of Technology, 71555-313, Shiraz, Iran

    Mohammad Navid Soltani Rad, Somayeh Behrouz, Marzieh Behrouz & Akram Sami

  2. Fasa University of Medical Sciences, Fasa, Iran

    Mehdi Mardkhoshnood, Ali Zarenezhad & Elham Zarenezhad

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  1. Mohammad Navid Soltani Rad
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Rad, M.N.S., Behrouz, S., Behrouz, M. et al. Design, synthesis and biological evaluation of novel 1,2,3-triazolyl \(\upbeta \)-hydroxy alkyl/carbazole hybrid molecules. Mol Divers 20, 705–718 (2016). https://doi.org/10.1007/s11030-016-9678-7

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