Koh Augustine Jing Jie, Thombare Varsha, Hussein Maytham, Rao Gauri G, Li Jian, Velkov Tony
Department of Biochemistry and Pharmacology, School of Biomedical Sciences, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Parkville, VIP, Australia.
Monash Biomedicine Discovery Institute, Department of Pharmacology, Monash University, Parkville, VIP, Australia.
Front Pharmacol. 2023 Jun 12;14:1158152. doi: 10.3389/fphar.2023.1158152. eCollection 2023.
Antibiotic resistance is a top threat to human health and a priority across the globe. This problematic issue is accompanied by the decline of new antibiotics in the pipeline over the past 30 years. In this context, an urgent need to develop new strategies to combat antimicrobial resistance is in great demand. Lately, among the possible approaches used to deal with antimicrobial resistance is the covalent ligation of two antibiotic pharmacophores that target the bacterial cells through a dissimilar mode of action into a single hybrid molecule, namely hybrid antibiotics. This strategy exhibits several advantages, including better antibacterial activity, overcoming the existing resistance towards individual antibiotics, and may ultimately delay the onset of bacterial resistance. This review sheds light on the latest development of the dual antibiotic hybrids pipeline, their potential mechanisms of action, and challenges in their use.
抗生素耐药性是对人类健康的首要威胁，也是全球的优先事项。这个问题伴随着过去30年中处于研发阶段的新型抗生素数量的减少。在这种背景下，迫切需要制定新的策略来对抗抗菌药物耐药性。最近，在用于应对抗菌药物耐药性的可能方法中，有一种是将两种通过不同作用方式靶向细菌细胞的抗生素药效基团共价连接成一个单一的杂合分子，即杂合抗生素。这种策略具有几个优点，包括更好的抗菌活性、克服对单一抗生素的现有耐药性，并且最终可能延缓细菌耐药性的出现。本综述阐述了双抗生素杂合体研发的最新进展、它们潜在的作用机制以及使用中的挑战。
