Si Zhangyong, Pethe Kevin, Chan-Park Mary B
School of Chemistry, Chemical Engineering and Biotechnology, Nanyang Technological University, Singapore 637459.
Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 636921.
JACS Au. 2023 Jan 31;3(2):276-292. doi: 10.1021/jacsau.2c00532. eCollection 2023 Feb 27.
The antimicrobial resistance crisis is a global health issue requiring discovery and development of novel therapeutics. However, conventional screening of natural products or synthetic chemical libraries is uncertain. Combination therapy using approved antibiotics with inhibitors targeting innate resistance mechanisms provides an alternative strategy to develop potent therapeutics. This review discusses the chemical structures of effective β-lactamase inhibitors, outer membrane permeabilizers, and efflux pump inhibitors that act as adjuvant molecules of classical antibiotics. Rational design of the chemical structures of adjuvants will provide methods to impart or restore efficacy to classical antibiotics for inherently antibiotic-resistant bacteria. As many bacteria have multiple resistance pathways, adjuvant molecules simultaneously targeting multiple pathways are promising approaches to combat multidrug-resistant bacterial infections.
抗菌药物耐药性危机是一个全球性的健康问题，需要发现和开发新型治疗方法。然而，对天然产物或合成化学文库进行传统筛选具有不确定性。将已批准的抗生素与靶向固有耐药机制的抑制剂联合使用，为开发有效的治疗方法提供了一种替代策略。本文综述了作为经典抗生素佐剂分子的有效β-内酰胺酶抑制剂、外膜通透剂和外排泵抑制剂的化学结构。合理设计佐剂的化学结构将为赋予或恢复经典抗生素对固有耐药细菌的疗效提供方法。由于许多细菌具有多种耐药途径，同时靶向多种途径的佐剂分子是对抗多重耐药细菌感染的有前景的方法。
