Antibacterial activity evaluation of vinyl sulfones against global predominant methicillin-resistant Staphylococcus...

Area of Science:

• Medicinal Chemistry
• Microbiology
• Drug Discovery

Background:

• Cysteine proteinases are crucial for Staphylococcus aureus (S. aureus) survival and pathogenesis, including the global health threat methicillin-resistant S. aureus (MRSA).
• Vinyl sulfones can rapidly capture cysteine-containing proteins under physiological conditions, suggesting potential as therapeutic agents.

Purpose of the Study:

• To synthesize and evaluate novel vinyl sulfone derivatives for antibacterial activity against pathogenic bacteria, including MRSA.
• To identify structure-activity relationships and elucidate the mechanism of action for potent antibacterial vinyl sulfones.

Main Methods:

• Synthesis of 28 vinyl sulfone derivatives.
• Susceptibility testing against pathogenic bacteria, including MRSA USA300 (SF8300).
• Structure-activity relationship analysis and assessment of host cell adhesion inhibition.

Main Results:

• Discovery of several antibacterial vinyl sulfone derivatives.
• Nitrile-substituted vinyl phenyl sulfones exhibited potent antibacterial activity.
• (E)-3-((4-methoxyphenyl)sulfonyl)acrylonitrile showed the strongest potency with minimum inhibitory concentrations (MICs) of 1.875 µg/mL against S. aureus and 3.75 µg/mL against MRSA USA300.
• Antibacterial activity may involve sulfhydryl conjugation, and compounds impaired host cell adhesion.

Conclusions:

• Novel vinyl sulfones, especially nitrile-substituted derivatives, possess significant antibacterial potential against S. aureus and MRSA.
• These compounds represent promising candidates for the development of new therapeutics targeting S. aureus and MRSA infections.