Halogenated Antimicrobial Agents to Combat Drug-Resistant Pathogens

Abstract

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 post-antibiotic era. Significance StatementAntimicrobial 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 abilities to overcome antimicrobial resistance.

Enhancing the Bioavailability of Resveratrol: Combine It, Derivatize It, or Encapsulate It?

“…The addition of a halogen group to RSV might increase its therapeutic potential ( Figure 6 ) [ 145 ]. Interestingly, the (E)-2,6-dibromo-4-(3,5-dibromostyryl)phenol RSV derivative showed greater bioavailability than the parent RSV compound.…”

Antibacterial and antibiofilm activity of halogenated phenylboronic acids against Vibrio parahaemolyticus and Vibrio harveyi

“…The characterization of this behavior has been elucidated based on molecular level of electrostatic impending surfaces ( Cavallo et al., 2016 ). In addition, extensive research has examined the impact of halogenation, specifically bromination, chlorination, and iodination, on antimicrobial activity ( Faleye et al., 2024 ). The halogenation process is a valuable approach for manipulating the characteristics of biologically active compounds, particularly antimicrobial agents or example, boronic acids are intrinsically reactive yet stable and have low toxicity ( Jia et al., 2019 ; Faleye et al., 2024 ).…”

“…In addition, extensive research has examined the impact of halogenation, specifically bromination, chlorination, and iodination, on antimicrobial activity ( Faleye et al., 2024 ). The halogenation process is a valuable approach for manipulating the characteristics of biologically active compounds, particularly antimicrobial agents or example, boronic acids are intrinsically reactive yet stable and have low toxicity ( Jia et al., 2019 ; Faleye et al., 2024 ). Boronic acids are bioisosteres of carboxylic acids because they have the same period as carbon.…”

Antibacterial and antibiofilm activities of iodinated hydrocarbons against Vibrio parahaemolyticus and Staphylococcus aureus

“…In our previous studies, we established that straight chain fatty acids as well as halogenated derivatives of natural compounds including iodinated derivatives possessed antibiofilm potentials 20 – 24 . Halogenation has been employed to improve intracellular delivery, metabolic stability, enhance target binding affinity, and potentiate antimicrobial activities 25 , 26 . Therefore, we hypothesized that halogenated hydrocarbons may be viable alternative for biofilm control.…”