Structure-Activity Relationship, Cytotoxicity and Mode of Action of 2-Ester-substituted 1,5-Benzothiazepines as Potent Antifungal Agents

Authors

  • Wang Kang,

    1. College of Chemistry & Material Science, Hebei Normal University, Shijiazhuang, Hebei 050024, China
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  • Xingqiong Du,

    1. College of Life Sciences, Hebei Normal University, Shijiazhuang, Hebei 050024, China
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  • Lanzhi Wang,

    1. College of Chemistry & Material Science, Hebei Normal University, Shijiazhuang, Hebei 050024, China
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  • Lijuan Hu,

    1. College of Chemistry & Material Science, Hebei Normal University, Shijiazhuang, Hebei 050024, China
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  • Yuhuan Dong,

    1. Department of Chemistry, Tangshan Normal University, Tangshan, Hebei 063000, China
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  • Yanqing Bian,

    Corresponding author
    1. College of Life Sciences, Hebei Normal University, Shijiazhuang, Hebei 050024, China
    • Yanqing Bian, College of Life Sciences, Hebei Normal University, Shijiazhuang, Hebei 050024, China

      Yuan Li, College of Chemistry & Material Science, Hebei Normal University, Shijiazhuang, Hebei 050024, China, Tel.: 0086-0311-80787400

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  • Yuan Li

    Corresponding author
    1. College of Chemistry & Material Science, Hebei Normal University, Shijiazhuang, Hebei 050024, China
    • Yanqing Bian, College of Life Sciences, Hebei Normal University, Shijiazhuang, Hebei 050024, China

      Yuan Li, College of Chemistry & Material Science, Hebei Normal University, Shijiazhuang, Hebei 050024, China, Tel.: 0086-0311-80787400

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Abstract

Our studies examined the structural features responsible for the antifungal activity of 2-ethoxycarbonyl-1,5-benzothiazepine (7a). Three series of 1,5-benzothiazepine derivatives were synthesized and screened for their antifungal activity. The results suggested that the ethoxycarbonyl group at the 2 position and the imine moiety on the seven-membered ring are essential for activity. The most potent of the synthesized analogues (7a, 7b) were further studied by evaluating their cytotoxicity and mode of action (for 7a). The results showed that compounds 7a and 7b were relatively safe for BV2 cells, but compound 7a interfered with Cryptococcus neoformans cell wall integrity by increasing the chitinase activity. Therefore, compound 7a was considered safe as an antifungal agent for animal cells.

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