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Licensed Unlicensed Requires Authentication Published by De Gruyter May 15, 2015

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

  • Martin Krátký EMAIL logo , Jana Mandíková , František Trejtnar , Vladimír Buchta , Jiřina Stolaříková and Jarmila Vinšová
From the journal Chemical Papers


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.


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Received: 2014-12-26
Revised: 2015-2-1
Accepted: 2015-2-7
Published Online: 2015-5-15
Published in Print: 2015-8-1

© Institute of Chemistry, Slovak Academy of Sciences

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