Halogenated Antimicrobial Agents to Combat Drug-Resistant Pathogens.

Area of Science:

• Medicinal Chemistry
• Pharmacology
• Microbiology

Background:

• Antimicrobial resistance (AMR) poses a significant global health threat, diminishing the efficacy of conventional antibiotics.
• Halogen atoms have historically played a role in antimicrobial agent development.
• Understanding the impact of halogens on antimicrobial properties is vital for developing new therapeutic strategies.

Purpose of the Study:

• To comprehensively review the role of halogen atoms in antibiotic scaffolds and their impact on antimicrobial activity.
• To explore structure-activity relationships and mechanisms of action influenced by halogenation.
• To assess the potential of halogenation in overcoming antimicrobial resistance and rejuvenating existing antibiotics.

Main Methods:

• Literature review of existing studies on halogenated antimicrobial agents.
• Analysis of diverse antimicrobial scaffolds incorporating halogens (e.g., carbohydrates, peptides, lipids).
• Evaluation of halogenation's effects on pharmacokinetics, pharmacodynamics, and antivirulence activities.

Main Results:

• Halogen atoms significantly influence antimicrobial activity, drug resistance profiles, and pharmacokinetic/pharmacodynamic properties.
• Halogenation can enhance the efficacy of existing antibiotics and potentially circumvent resistance mechanisms.
• Various halogenated molecules, including complex structures, demonstrate therapeutic potential.

Conclusions:

• Halogenation is a key strategy for enhancing antimicrobial drug efficacy and combating resistance.
• Further research into halogenated scaffolds offers promising avenues for developing novel therapeutics to prevent a postantibiotic era.
• This review highlights the established and emerging roles of halogens in antimicrobial drug design and development.