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Chemical Papers

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Volume 69, Issue 8

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

Martin Krátký
  • Corresponding author
  • Department of Inorganic and Organic Chemistry, Faculty of Pharmacy, Charles University in Prague, Heyrovského 1203, 500 05 Hradec Králové, Czech Republic
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/ Jana Mandíková
  • Department of Pharmacology and Toxicology, Faculty of Pharmacy, Charles University in Prague, Heyrovského 1203, 500 05 Hradec Králové, Czech Republic
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  • De Gruyter OnlineGoogle Scholar
/ František Trejtnar
  • Department of Pharmacology and Toxicology, Faculty of Pharmacy, Charles University in Prague, Heyrovského 1203, 500 05 Hradec Králové, Czech Republic
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/ Vladimír Buchta
  • Department of Biological and Medical Sciences, Faculty of Pharmacy, Charles University in Prague, Heyrovského 1203, 500 05 Hradec Králové, Czech Republic
  • Department of Clinical Microbiology, Faculty of Medicine and University Hospital, Charles University in Prague, Sokolská 581, 500 12 Hradec Králové, Czech Republic
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/ Jiřina Stolaříková
  • Laboratory for Mycobacterial Diagnostics and Tuberculosis, Regional Institute of Public Health in Ostrava, Partyzánské náměstí 7, 702 00 Ostrava, Czech Republic
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/ Jarmila Vinšová
  • Department of Inorganic and Organic Chemistry, Faculty of Pharmacy, Charles University in Prague, Heyrovského 1203, 500 05 Hradec Králové, Czech Republic
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Published Online: 2015-05-15 | DOI: https://doi.org/10.1515/chempap-2015-0109

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 methicillinresistant 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.

Keywords: antimicrobial activity; antimycobacterial activity; imidazolidine-2,4,5-triones; sulphamethoxazole; ureas

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About the article

Received: 2014-12-26

Revised: 2015-02-01

Accepted: 2015-02-07

Published Online: 2015-05-15

Published in Print: 2015-08-01


Citation Information: Chemical Papers, Volume 69, Issue 8, Pages 1108–1117, ISSN (Online) 1336-9075, ISSN (Print) 0366-6352, DOI: https://doi.org/10.1515/chempap-2015-0109.

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