Reinke T. Müller

Abstract In many Gram-negative bacteria such as Escherichia coli and Klebsiella pneumoniae, the AcrAB-TolC efflux pump is central to multidrug resistance. We report the development of BDM91531, a nanomolar pyridylpiperazine inhibitor that potentiates the activity of several antibiotics.

3.8. Pyridylpiperazines (BDM Compounds) Pyridylpiperazine compounds have been recently described as AcrB inhibitors and are able to boost antibiotic activity in E. coli [83]. BDM88855 (78) and derivatives act as allosteric efflux-pump inhibitors, which uniquely bind to the transmembrane domain of AcrB. This series was discovered by phenotypic screening of a 1280 fragment-library on E. coli BW25113 in combination with a sub-active dose of pyridomycin, a compound particularly effluxed by AcrAB-TolC.