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Synthesis and antimicrobial activity of sulphamethoxazole-based ureas and imidazolidine-2,4,5-triones

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Abstract

Progression of drug resistance among bacterial and fungal pathogens justifies the development of novel antimicrobial agents. Thus, a series of novel sulphamethoxazole-based ureas and imidazolidine-2,4,5-triones have been designed and synthesised. The urea derivatives were obtained by the reaction of sulphamethoxazole and isocyanates, and their cyclisation to imidazolidine-2,4,5-triones was performed via oxalyl chloride. All synthesised derivatives were evaluated in vitro to determine their activity against gram-positive and gram-negative bacteria, fungi, Mycobacterium tuberculosis, and atypical mycobacteria and their cytotoxicity. The growth of mycobacteria was inhibited within the range of 4–1000 µM and M. tuberculosis was the least-susceptible strain. 4-(3-Heptylureido)-N-(5-methylisoxazol-3-yl)benzenesulphonamide was identified as the most promising compound because it exhibited the highest activity against atypical mycobacteria at minimum inhibitory concentrations, from 4 µM, and with acceptable toxicity (selectivity indices for M. avium and M. kansasii higher than 16 and 62.5, respectively). Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus, were inhibited at concentrations starting from 125 µM, whereas the investigated derivatives exhibited almost no antifungal potency and activity against gram-negative species.

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Authors and Affiliations

  1. Department of Inorganic and Organic Chemistry, Faculty of Pharmacy, Charles University in Prague, Heyrovského 1203, 500 05, Hradec Králové, Czech Republic

    Martin Krátký & Jarmila Vinšová

  2. Department of Pharmacology and Toxicology, Faculty of Pharmacy, Charles University in Prague, Heyrovského 1203, 500 05, Hradec Králové, Czech Republic

    Jana Mandíková & František Trejtnar

  3. Department of Biological and Medical Sciences, Faculty of Pharmacy, Charles University in Prague, Heyrovského 1203, 500 05, Hradec Králové, Czech Republic

    Vladimír Buchta

  4. Department of Clinical Microbiology, Faculty of Medicine and University Hospital, Charles University in Prague, Sokolská 581, 500 12, Hradec Králové, Czech Republic

    Vladimír Buchta

  5. Laboratory for Mycobacterial Diagnostics and Tuberculosis, Regional Institute of Public Health in Ostrava, Partyzánské náměstí 7, 702 00, Ostrava, Czech Republic

    Jiřina Stolaříková

Authors
  1. Martin Krátký
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  2. Jana Mandíková
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  3. František Trejtnar
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  4. Vladimír Buchta
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  5. Jiřina Stolaříková
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  6. Jarmila Vinšová
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Correspondence to Martin Krátký.

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Krátký, M., Mandíková, J., Trejtnar, F. et al. Synthesis and antimicrobial activity of sulphamethoxazole-based ureas and imidazolidine-2,4,5-triones. Chem. Pap. 69, 1108–1117 (2015). https://doi.org/10.1515/chempap-2015-0109

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  • DOI: https://doi.org/10.1515/chempap-2015-0109

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