Discovery of a novel AcrAB-TolC pump inhibitor using the multistep virtual screening, synthesis and biological evaluation of asymmetric imidazole-4,5-dicarboxamide derivatives

Asymmetric imidazole-4-5-dicarboxamide derivatives targeting AcrAB-TolC, a drug-resistant pump in E. coli, were identified using multistep screening. Novel compounds with the morpholine moiety were synthesized and tested for their ability to inhibit AcrB in vitro and to predict their pharmacokinetic properties. Our findings may aid the design and development of effective inhibitors. By virtual screening, we identify the potential of asymmetric imidazole-4,5-dicarboxamide derivatives as E. coli-AcrB efflux pump inhibitors. The compounds are synthesized and their inhibitory activity is evaluated by a biological assay.

Automated summary

By multistep screening, novel asymmetric imidazole-4,5-dicarboxamide derivatives targeting the drug-resistant pump AcrAB-TolC in E. coli were identified. The synthesized compounds with the morpholine moiety showed inhibitory activity against AcrB in vitro and exhibited promising pharmacokinetic properties.