Dias Catarina, Rauter Amélia P
Centro de Química e Bioquímica, Faculdade de Ciências, Universidade de Lisboa, Lisboa, Portugal.
Centro de Química Estrutural, Faculdade de Ciências, Universidade de Lisboa, Lisboa, Portugal.
Future Med Chem. 2019 Feb;11(3):211-228. doi: 10.4155/fmc-2018-0254. Epub 2019 Feb 25.
The rise of antibiotic resistant bacteria requires unconventional strategies toward efficient chemotherapeutic agents, preferably with alternative mechanisms of action. The bacterial cell membrane has become an appealing target since its essential and highly conservative structure are key challenges to resistance mechanisms. Inspired by natural antimicrobial peptides, research on membrane-targeting antimicrobials has been growing out of the peptide space. The pursuit of more druggable molecules led to the discovery that the pharmacophore of antimicrobial peptides is smaller than anticipated. Several promising classes of membrane-targeting antimicrobials have been discovered, such as ceragenins, reutericyclines, carbohydrate amphiphiles - among others. This review will discuss the most recent findings on membrane-targeting antibiotics, focusing on small molecules outside the antimicrobial peptide molecular space.
抗生素耐药细菌的出现需要采用非常规策略来研发高效化疗药物，最好具有替代作用机制。细菌细胞膜已成为一个有吸引力的靶点，因为其基本且高度保守的结构是耐药机制面临的关键挑战。受天然抗菌肽的启发，针对膜靶向抗菌剂的研究已从肽领域拓展开来。对更具成药性分子的追求导致发现抗菌肽的药效基团比预期的要小。已经发现了几类有前景的膜靶向抗菌剂，如杀菌素、罗伊氏环素、碳水化合物两亲物等。本综述将讨论膜靶向抗生素的最新研究成果，重点关注抗菌肽分子空间之外的小分子。
