School of Chemical Engineering (O.S.F., B.R.B., J.-H.L., J.L.) and Department of Medical Biotechnology (I.C.), Yeungnam University, Gyeongsan, Republic of Korea.
School of Chemical Engineering (O.S.F., B.R.B., J.-H.L., J.L.) and Department of Medical Biotechnology (I.C.), Yeungnam University, Gyeongsan, Republic of Korea
Pharmacol Rev. 2023 Dec 15;76(1):90-141. doi: 10.1124/pharmrev.123.000863.
Antimicrobial resistance presents us with a potential global crisis as it undermines the abilities of conventional antibiotics to combat pathogenic microbes. The history of antimicrobial agents is replete with examples of scaffolds containing halogens. In this review, we discuss the impacts of halogen atoms in various antibiotic types and antimicrobial scaffolds and their modes of action, structure-activity relationships, and the contributions of halogen atoms in antimicrobial activity and drug resistance. Other halogenated molecules, including carbohydrates, peptides, lipids, and polymeric complexes, are also reviewed, and the effects of halogenated scaffolds on pharmacokinetics, pharmacodynamics, and factors affecting antimicrobial and antivirulence activities are presented. Furthermore, the potential of halogenation to circumvent antimicrobial resistance and rejuvenate impotent antibiotics is addressed. This review provides an overview of the significance of halogenation, the abilities of halogens to interact in biomolecular settings and enhance pharmacological properties, and their potential therapeutic usages in preventing a postantibiotic era. SIGNIFICANCE STATEMENT: Antimicrobial resistance and the increasing impotence of antibiotics are critical threats to global health. The roles and importance of halogen atoms in antimicrobial drug scaffolds have been established, but comparatively little is known of their pharmacological impacts on drug resistance and antivirulence activities. This review is the first to extensively evaluate the roles of halogen atoms in various antibiotic classes and pharmacological scaffolds and to provide an overview of their ability to overcome antimicrobial resistance.
抗微生物药物耐药性对全球健康构成潜在的全球性危机，因为它破坏了常规抗生素对抗致病微生物的能力。含卤素的抗菌药物支架在抗菌药物历史中比比皆是。在这篇综述中，我们讨论了卤素原子在各种抗生素类型和抗菌支架中的作用及其作用模式、构效关系，以及卤素原子在抗菌活性和耐药性中的作用。还综述了其他含卤素分子，包括碳水化合物、肽、脂质和聚合复合物，并介绍了卤素支架对药代动力学、药效学以及影响抗菌和抗毒力活性的因素的影响。此外，还探讨了卤化作用克服抗微生物药物耐药性和恢复无效抗生素的潜力。本综述概述了卤化作用的重要性、卤素在生物分子环境中相互作用和增强药理特性的能力，以及它们在预防后抗生素时代中的潜在治疗用途。
抗微生物药物耐药性和抗生素效力的日益下降是对全球健康的重大威胁。卤素原子在抗菌药物支架中的作用和重要性已经确立，但它们对耐药性和抗病毒活性的药理影响知之甚少。这是第一篇广泛评估各种抗生素类别和药理支架中卤素原子作用的综述，并概述了它们克服抗微生物药物耐药性的能力。
