Overcoming multidrug resistance in microbials using nanostructures self-assembled from cationic bent-core oligomers

Area of Science:

• Supramolecular Chemistry
• Materials Science
• Antimicrobial Research

Background:

• The rise of multidrug-resistant bacteria, such as Methicillin-resistant Staphylococcus aureus (MRSA), necessitates the development of novel therapeutic agents.
• Cationic molecules and self-assembled nanostructures are promising platforms for antimicrobial drug discovery.
• Terephthalamide-bisurea scaffolds offer a rigid core for designing functional molecules.

Purpose of the Study:

• To synthesize and characterize novel cationic molecules based on terephthalamide-bisurea cores.
• To investigate the self-assembly behavior of these molecules in aqueous media.
• To evaluate the antimicrobial activity and selectivity of the self-assembled nanostructures against clinically relevant bacteria, including MRSA.

Main Methods:

• Synthesis of terephthalamide-bisurea derivatives functionalized with imidazolium groups.
• Characterization of molecular structures using spectroscopic techniques.
• Investigation of self-assembly into nanostructures using techniques like dynamic light scattering and electron microscopy.
• Antimicrobial activity assays against bacterial strains, including MRSA.
• Determination of selectivity and assessment of drug-resistance induction.

Main Results:

• Novel cationic molecules with terephthalamide-bisurea cores and imidazolium moieties were successfully synthesized.
• These compounds self-assemble in aqueous media to form supramolecular nanostructures with diverse morphologies.
• The optimized compound exhibited potent antimicrobial activity and high selectivity against clinical MRSA isolates.
• No significant drug-resistance was observed with the developed nanostructures.

Conclusions:

• Self-assembled cationic nanostructures derived from terephthalamide-bisurea cores represent a promising new class of antimicrobial agents.
• These nanostructures demonstrate potent and selective activity against MRSA without inducing resistance.
• The findings suggest potential applications in preventing and treating multidrug-resistant bacterial infections.