What is the antibacterial mechanism of riccardin C derivatives against MRSA?

Riccardin C derivatives, such as RC-112, AA-99, and AA-100, have been reported to exhibit anti-MRSA (methicillin-resistant Staphylococcus aureus) activity. However, the specific mechanism of action of these compounds was not clearly understood.

The antibacterial mechanism of riccardin C derivatives, such as RC-112, involves increasing the membrane permeability of MRSA cells to ethidium, propidium, Na+, and K+, leading to cell leakage and ultimately causing cell death. This is supported by the observation that these compounds caused the inflow and outflow of ethidium and propidium, as well as changes in intracellular ion concentrations. Additionally, transmission electron microscopy revealed the presence of intracellular lamellar mesosomal-like structures in treated cells, indicating membrane damage. Riccardin C derivatives induce cell leakage by increasing membrane permeability, which is a different mechanism from that of IDPO-9, which inhibits FabI.