Carro Laura
School of Pharmacy, University of East Anglia, Norwich Research Park, Norwich NR4 7TJ, UK.
Beilstein J Org Chem. 2018 Nov 21;14:2881-2896. doi: 10.3762/bjoc.14.267. eCollection 2018.
Antibiotics are potent pharmacological weapons against bacterial infections; however, the growing antibiotic resistance of microorganisms is compromising the efficacy of the currently available pharmacotherapies. Even though antimicrobial resistance is not a new problem, antibiotic development has failed to match the growth of resistant pathogens and hence, it is highly critical to discover new anti-infective drugs with novel mechanisms of action which will help reducing the burden of multidrug-resistant microorganisms. Protein-protein interactions (PPIs) are involved in a myriad of vital cellular processes and have become an attractive target to treat diseases. Therefore, targeting PPI networks in bacteria may offer a new and unconventional point of intervention to develop novel anti-infective drugs which can combat the ever-increasing rate of multidrug-resistant bacteria. This review describes the progress achieved towards the discovery of molecules that disrupt PPI systems in bacteria for which inhibitors have been identified and whose targets could represent an alternative lead discovery strategy to obtain new anti-infective molecules.
抗生素是对抗细菌感染的有力药理学武器;然而,微生物对抗生素的耐药性不断增强,正在削弱当前可用药物疗法的疗效。尽管抗菌耐药性并非新问题,但抗生素研发未能跟上耐药病原体的增长速度,因此,发现具有新作用机制的新型抗感染药物至关重要,这将有助于减轻多重耐药微生物的负担。蛋白质-蛋白质相互作用(PPI)参与众多重要的细胞过程,已成为治疗疾病的一个有吸引力的靶点。因此,针对细菌中的PPI网络可能提供一个新的、非常规的干预点,以开发能够对抗不断增加的多重耐药细菌发生率的新型抗感染药物。本综述描述了在发现破坏细菌PPI系统的分子方面所取得的进展,已鉴定出这些分子的抑制剂,其靶点可能代表一种替代的先导物发现策略,以获得新的抗感染分子。