title: 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.
authors.affiliation: Drug Delivery, Disposition and Dynamics, ‡Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University , 381 Royal Parade, Parkville 3052, Victoria, Australia.
authors.forename: Tony
authors.initials: T
authors.lastname: Velkov
authors.forename: Kade D
authors.initials: KD
authors.lastname: Roberts
authors.forename: Roger L
authors.initials: RL
authors.lastname: Nation
authors.forename: Jiping
authors.initials: J
authors.lastname: Wang
authors.forename: Philip E
authors.initials: PE
authors.lastname: Thompson
authors.forename: Jian
authors.initials: J
authors.lastname: Li
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D024901:Drug Resistance, Multiple, Bacterial; D006090:Gram-Negative Bacteria / Q000187:drug effects*; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy; D006801:Humans; D051379:Mice; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D011113:Polymyxins / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D011552:Pseudomonas Infections / Q000188:drug therapy; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D011113:Polymyxins