Chemical modulation of the biological activity of reutericyclin: a membrane-active antibiotic from Lactobacillus reuteri.

ABSTRACT: Whilst the development of membrane-active antibiotics is now an attractive therapeutic concept, progress in this area is disadvantaged by poor knowledge of the structure-activity relationship (SAR) required for optimizing molecules to selectively target bacteria. This prompted us to explore the SAR of the Lactobacillus reuteri membrane-active antibiotic reutericyclin, modifying three key positions about its tetramic acid core. The SAR revealed that lipophilic analogs were generally more active against Gram-positive pathogens, but introduction of polar and charged substituents diminished their activity. This was confirmed by cytometric assays showing that inactive compounds failed to dissipate the membrane potential. Radiolabeled substrate assays indicated that dissipation of the membrane p

SUBMITTER: Cherian PT 

PROVIDER: S-EPMC4894453 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature