School of Life Sciences, Centre for Biomolecular Sciences , University of Nottingham , Nottingham , NG7 2RD , U.K.
School of Pharmacy, Centre for Biomolecular Sciences , University of Nottingham , Nottingham , NG7 2RD , U.K.
J Med Chem. 2018 Dec 13;61(23):10385-10402. doi: 10.1021/acs.jmedchem.8b00540. Epub 2018 Jul 27.
Antimicrobial resistance (AMR) is a serious threat to public health globally, manifested by the frequent emergence of multidrug resistant pathogens that render current chemotherapy inadequate. Health organizations worldwide have recognized the severity of this crisis and implemented action plans to contain its adverse consequences and prolong the utility of conventional antibiotics. Hence, there is a pressing need for new classes of antibacterial agents with novel modes of action. Quorum sensing (QS), a communication system employed by bacterial populations to coordinate virulence gene expression, is a potential target that has been intensively investigated over the past decade. This Perspective will focus on recent advances in targeting the three main quorum sensing systems ( las, rhl, and pqs) of a major opportunistic human pathogen, Pseudomonas aeruginosa, and will specifically evaluate the medicinal chemistry strategies devised to develop QS inhibitors from a drug discovery perspective.
抗微生物药物耐药性（AMR）是全球公共卫生面临的严重威胁，其表现为经常出现使当前化疗无效的多药耐药病原体。全球卫生组织已经认识到这一危机的严重性，并实施了行动计划，以遏制其不良后果并延长常规抗生素的使用。因此，迫切需要具有新型作用模式的新型抗菌药物。群体感应（QS）是细菌种群用来协调毒力基因表达的一种通讯系统，是过去十年中受到广泛关注的一个潜在靶点。本观点将重点介绍靶向主要机会性病原体铜绿假单胞菌的三个主要群体感应系统（las、rhl 和 pqs）的最新进展，并从药物发现的角度具体评估为开发 QS 抑制剂而设计的药物化学策略。
