Institute of Drug Discovery and Design, College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, Hangzhou, Zhejiang 310058, P. R. China.
Department of Chemistry, University of South Florida, 4202 E. Fowler Avenue, Tampa, Florida 33620, United States.
J Med Chem. 2023 Feb 23;66(4):2211-2234. doi: 10.1021/acs.jmedchem.2c00757. Epub 2023 Feb 5.
Clinically, antibiotics are widely used to treat infectious diseases; however, excessive drug abuse and overuse exacerbate the prevalence of drug-resistant bacterial pathogens, making the development of novel antibiotics extremely difficult. Antimicrobial peptide (AMP) is one of the most promising candidates for overcoming bacterial resistance owing to its unique structure and mechanism of action. This study examines the development of small molecular mimetics of AMPs over the past two decades. These mimetics can selectively disrupt membranes, which are the characteristic antibacterial mechanism of AMPs. In addition, the advantages and disadvantages of small AMP mimetics are discussed. The small molecular mimetics of AMPs are anticipated to garner interest and investment in discovering new antibiotics. This Perspective will assist in revitalizing the golden age of antibiotics in the current era of combating bacterial resistance.
临床上，抗生素被广泛用于治疗传染病；然而，过度滥用和过度使用会加剧耐药细菌病原体的流行，使得新型抗生素的开发变得极其困难。抗菌肽 (AMP) 是克服细菌耐药性最有前途的候选物之一，因为其独特的结构和作用机制。本研究考察了过去二十年中 AMP 的小分子模拟物的发展。这些模拟物可以选择性地破坏细胞膜，这是 AMP 的特征性抗菌机制。此外，还讨论了小分子 AMP 模拟物的优缺点。预计 AMP 的小分子模拟物将引起人们对发现新型抗生素的兴趣和投资。本观点将有助于在当前对抗细菌耐药性的时代重振抗生素的黄金时代。
