Abstract
Objectives
The study aimed to characterise compounds with activity against carbapenemase-expressing Gram-negative bacteria and nematodes, with the intention that the compounds would lack cytotoxicity against non-cancer human cells.
Methods
The antimicrobial activity and toxicity to nematodes and human cell lines of a series of phenyl substituted urea derivatives were evaluated using Minimum Inhibitory Concentration (MIC), 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 (CPE) 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 multi-drug resistant E. coli strain were 100, 50 and 36 μM (32, 16 and 16 mg/L), for the same compounds. 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-cancer human cell lines suggested that some of the compounds have potential to affect bacteria and especially helminths with limited cytotoxicity for humans. Given the simplicity of synthesis for this class of compound and the potency against a Gram-negative carbapenemase-expressing Klebsiella pneumoniae, aryl ureas possessing the 3,5-dichloro-phenyl group certainly warrant further investigation to exploit their selectivity.
The study aimed to characterise compounds with activity against carbapenemase-expressing Gram-negative bacteria and nematodes, with the intention that the compounds would lack cytotoxicity against non-cancer human cells.
Methods
The antimicrobial activity and toxicity to nematodes and human cell lines of a series of phenyl substituted urea derivatives were evaluated using Minimum Inhibitory Concentration (MIC), 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 (CPE) 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 multi-drug resistant E. coli strain were 100, 50 and 36 μM (32, 16 and 16 mg/L), for the same compounds. 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-cancer human cell lines suggested that some of the compounds have potential to affect bacteria and especially helminths with limited cytotoxicity for humans. Given the simplicity of synthesis for this class of compound and the potency against a Gram-negative carbapenemase-expressing Klebsiella pneumoniae, aryl ureas possessing the 3,5-dichloro-phenyl group certainly warrant further investigation to exploit their selectivity.
| Original language | English |
|---|---|
| Journal | Journal of Global Antimicrobial Resistance |
| Early online date | 10 Mar 2023 |
| DOIs | |
| Publication status | E-pub ahead of print - 10 Mar 2023 |
