Chalcones as Emerging Antibacterial Scaffolds: A Mini Review

Area of Science:

• Medicinal Chemistry
• Pharmacology
• Organic Chemistry

Background:

• Antimicrobial resistance (AMR) is a growing global health threat, necessitating the development of new antibacterial agents.
• Chalcones, aromatic ketones with a specific α, β-unsaturated carbonyl system, are emerging as promising scaffolds for novel antibacterial drug discovery.

Purpose of the Study:

• To comprehensively review chalcones as potent antibacterial agents.
• To explore their structural versatility, mechanisms of action, and therapeutic potential against various bacterial pathogens, including multidrug-resistant strains.

Main Methods:

• Literature review focusing on chalcone synthesis, structure-activity relationships (SAR), and mechanisms of action.
• Analysis of computational studies, including quantitative structure-activity relationship (QSAR) modeling and molecular docking.
• Examination of recent advancements in green synthesis methodologies for chalcone derivatives.

Main Results:

• Chalcones exhibit broad-spectrum antibacterial activity, including against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococci (VRE).
• Their antibacterial effects are mediated through multiple pathways, such as membrane disruption, inhibition of cell wall biosynthesis, DNA replication interference, and protein synthesis suppression.
• Specific chalcone derivatives, like compound 85 (MIC 3.4 nM), demonstrate potent activity, surpassing some existing antibiotics like ciprofloxacin (MIC 4.7 nM).

Conclusions:

• Chalcones are structurally versatile and biologically robust compounds with significant potential as adaptable antibacterial agents.
• Their ability to circumvent classical resistance mechanisms and their amenability to chemical optimization make them valuable in combating antimicrobial resistance.
• Advancements in synthesis and computational design facilitate the development of next-generation chalcone-based antimicrobials for future therapeutic applications.