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Novel derivatives of substituted 6-fluorobenzothiazole diamides: synthesis, antifungal activity and cytotoxicity

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Abstract

A new series of 1-[(1R)-1-(6-fluoro-1,3-benzothiazol-2-yl)ethyl]-3-substituted phenyl diamides were synthesized in vitro as potential antifungal agents. Chemical structures of the synthesised compounds were substantiated by IR, 1H, 13C, 19F nuclear magnetic resonance spectra, high resolution mass spectrometry, elemental analysis and also by X-ray diffraction. In addition, the cytotoxicity of the most active compounds was investigated against cancer cell line (Jurkat) and one type of normal lung fibroblast cells (MRC-5) by (2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide) tetrazolium salt reduction assay, propidium iodide flow cytometry assay and xCELLigence system allowing a label-free assessment of the cells proliferation. Compounds indicated as 11e, 11g, 11j, 11n and 11o, were the best of the series, showing minimum inhibitory concentration values of 6.25–50 μg/mL against pathogenic strains Candida albicans HE 169, Candida tropicalis 31/HK and Candida parapsilosis p69. Moreover compounds 11e, 11g, 11j and 11o did not show any cytotoxic effect against human Jurkat and MRC-5 cells.

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Authors and Affiliations

  1. Department of Biological and Biochemical Sciences, Faculty of Chemical Technology, University of Pardubice, Studentská 573, Pardubice, 532 10, Czech Republic

    Marcela Pejchalová, Radim Havelek & Karel Královec

  2. Department of General and Inorganic Chemistry, Faculty of Chemical Technology, University of Pardubice, Studentská 573, Pardubice, 532 10, Czech Republic

    Zdeňka Růžičková

  3. Institute of Organic Chemistry and Technology, Faculty of Chemical Technology, University of Pardubice, Studentská 573, Pardubice, 532 10, Czech Republic

    Vladimír Pejchal

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  1. Marcela Pejchalová
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  2. Radim Havelek
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  3. Karel Královec
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  4. Zdeňka Růžičková
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  5. Vladimír Pejchal
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Correspondence to Karel Královec.

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Pejchalová, M., Havelek, R., Královec, K. et al. Novel derivatives of substituted 6-fluorobenzothiazole diamides: synthesis, antifungal activity and cytotoxicity. Med Chem Res 26, 1847–1862 (2017). https://doi.org/10.1007/s00044-017-1894-x

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  • DOI: https://doi.org/10.1007/s00044-017-1894-x

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