让“老”多粘菌素发挥新作用：靶向革兰氏阴性“超级细菌”的新一代脂肽

Velkov Tony, Roberts Kade D, Nation Roger L, Wang Jiping, Thompson Philip E, Li Jian

Drug Delivery, Disposition and Dynamics, ‡Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University , 381 Royal Parade, Parkville 3052, Victoria, Australia.

ACS Chem Biol. 2014 May 16;9(5):1172-7. doi: 10.1021/cb500080r. Epub 2014 Mar 17.

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.

抗菌脂肽多粘菌素B和E（黏菌素）正被用作治疗多重耐药革兰氏阴性病原体引起感染的“最后一线”疗法。多粘菌素耐药意味着完全缺乏用于治疗由革兰氏阴性“超级细菌”引起的危及生命感染的抗生素。本报告详细介绍了基于构效关系（SAR）的设计、全合成以及一系列对多粘菌素耐药革兰氏阴性菌具有更好抗菌活性的新型多粘菌素脂肽的临床前评估。