Teaching 'old' polymyxins new tricks: New-generation lipopeptides targeting gram-negative 'superbugs'

Abstract

The antimicrobial lipopeptides polymyxin B and E (colistin) are being used as a last-line therapy for infections caused by multidrug-resistant Gram-negative pathogens. Polymyxin resistance implies a total lack of antibiotics for the treatment of life-threatening infections caused by the Gram-negative superbugs. This report details the structure-activity relationships (SAR) based design, in toto synthesis, and preclinical evaluation of a series of novel polymyxin lipopeptides with better antibacterial activity against polymyxin-resistant Gram-negative bacteria. © 2014 American Chemical Society.