# Antibacterial Activity of the Pyrazolone Copper Complex P-FAH-Cu-phen Against Staphylococcus aureus and Promotion of Healing of Traumatized Infected Skin in Mice

## TL;DR

A new copper complex, P-FAH-Cu-phen, effectively kills Staphylococcus aureus and promotes healing of infected skin wounds in mice.

## Contribution

The study introduces a novel pyrazolone copper complex with potent antibacterial activity and wound-healing properties.

## Key findings

- P-FAH-Cu-phen showed potent bactericidal activity with a MIC of 1.4 μg/mL and rapid killing of S. aureus.
- The compound reduced bacterial virulence and biofilm formation while promoting wound healing in mice.
- Topical application of P-FAH-Cu-phen accelerated wound closure and reduced inflammation markers in infected skin.

## Abstract

Staphylococcus aureus is a major cause of skin and soft tissue infections, necessitating the development of new topical agents with rapid bactericidal activity and low resistance potential. Here, we evaluated the antibacterial activity of a pyrazolone copper complex (P-FAH-Cu-phen) against S. aureus, investigated its in vitro mode of action, and its assessed therapeutic efficacy in a murine model of S. aureus-infected skin trauma. P-FAH-Cu-phen exhibited potent bactericidal activity (minimum inhibitory concentration [MIC] 1.4 μg/mL; minimum bactericidal concentration [MBC] 2.8 μg/mL) and rapid killing (>91% eradication within 2.5 min), with no detectable MIC increase under the tested serial passaging conditions. Cell-envelope dysfunction was evidenced by increased supernatant alkaline phosphatase activity, elevated leakage of nucleic acids and proteins, and reduced membrane-associated Na+/K+- and Ca2+/Mg2+-ATPase activities. At sub-inhibitory concentrations, P-FAH-Cu-phen reduced haemolytic and coagulase activities, modulated virulence gene expression (sea, hla, agrA), and inhibited biofilm formation and biofilm-associated metabolic activity. In vivo, topical treatment accelerated wound closure and histopathological repair, increased hydroxyproline content, reduced bacterial burden, and lowered TNF-α and IL-10 levels in wound tissues. Collectively, P-FAH-Cu-phen shows multi-faceted anti-infective activity and exhibits further development as a topical candidate for S. aureus-infected skin wounds.