New Antimicrobials Based on the Adarotene Scaffold with Activity against Multi-Drug Resistant Staphylococcus aureus...

Area of Science:

• Medicinal Chemistry
• Antimicrobial Resistance
• Drug Discovery

Background:

• Rising global infections caused by multi-drug resistant (MDR) pathogens pose a significant threat to public health.
• Existing treatments are becoming less effective against common bacterial infections.

Purpose of the Study:

• To investigate the antibacterial activity of adarotene-related synthetic retinoids against key pathogens.
• To explore the potential of these compounds as novel antimicrobial agents, particularly against MDR strains.

Main Methods:

• Synthesis and screening of a panel of adarotene-related synthetic retinoids.
• Determination of Minimum Inhibitory Concentrations (MICs) and bactericidal effects.
• Nuclear Magnetic Resonance (NMR) experiments to elucidate compound-membrane interactions.
• Biological assessment of antibacterial efficacy and selectivity.

Main Results:

• Several synthetic retinoids exhibited significant antibacterial activity against Staphylococcus aureus and Enterococcus faecalis, including MDR strains.
• Compounds demonstrated favorable MICs and a notable bactericidal effect.
• Modifications to the adarotene scaffold allowed for selectivity towards antibacterial activity over anticancer properties.
• NMR studies provided insights into the interaction of adarotene with microbial membranes.

Conclusions:

• The adarotene scaffold is a promising starting point for developing new non-toxic antimicrobials.
• Further development could lead to effective treatments against MDR bacterial strains.
• Synthetic retinoids offer a potential new class of antibiotics to combat antimicrobial resistance.