Antimicrobial and anthelmintic activities of aryl urea agents

0578552 - ÚEB 2024 RIV NL eng J - Journal Article
de Resende, P. E. - Nisler, Jaroslav - Voller, J. - Kadlecová, A. - Gibbons, S.
Antimicrobial and anthelmintic activities of aryl urea agents.
Journal of Global Antimicrobial Resistance. Roč. 33, JUN (2023), s. 114-119. ISSN 2213-7165. E-ISSN 2213-7173
Institutional support: RVO:61389030
Keywords : Anthelmintic * Antibacterial * Aryl urea * Caenorhabditis elegans * Carbapenemase
OECD category: Microbiology
Impact factor: 4.6, year: 2022
Method of publishing: Open access
https://doi.org/10.1016/j.jgar.2023.02.021

Objectives: This study aimed to characterise compounds with activity against carbapenemase-expressing Gram-negative bacteria and nematodes and evaluate their cytotoxicity to non-cancerous human cells. Methods: The antimicrobial activity and toxicity of a series of phenyl-substituted urea derivatives were evaluated using broth microdilution, chitinase, and resazurin reduction assays. Results: The effects of different substitutions present on the nitrogen atoms of the urea backbone were investigated. Several compounds were active against Staphylococcus aureus and Escherichia coli control strains. Specifically, derivatives 7b, 11b, and 67d exhibited antimicrobial activity against Klebsiella pneumoniae 16, a carbapenemase-producing Enterobacteriaceae species, with minimum inhibitory concentration (MIC) values of 100, 50, and 72 µM (32, 64, and 32 mg/L), respectively. In addition, the MICs obtained against a multidrug-resistant E. coli strain were 100, 50, and 36 µM (32, 16, and 16 mg/L) for the same compounds, respectively. Furthermore, the urea derivatives 18b, 29b, 50c, 51c, 52c, 55c–59c, and 62c were very active towards the nematode Caenorhabditis elegans. Conclusions: Testing on non-cancerous human cell lines suggested that some of the compounds have the potential to affect bacteria, especially helminths, with limited cytotoxicity to humans. Given the simplicity of synthesis for this class of compounds and their potency against Gram-negative, carbapenemase-expressing K. pneumoniae, aryl ureas possessing the 3,5-dichloro-phenyl group certainly warrant further investigation to exploit their selectivity.
Permanent Link: https://hdl.handle.net/11104/0347550