Antimicrobial and Antibiofilm Activity of Auranofin and Its Two Derivatives Bearing Naproxen and Acetylcysteine as Ligands Against Staphylococci.

: The ability of bacteria to form biofilms makes them more tolerant to traditional antibiotics. Given the lack of new antibiotic development, drug repurposing offers a strategy for discovering new treatments. Auranofin (AF), a gold-based compound indicated for the treatment of rheumatoid arthritis, shows promising antibacterial activity. This study investigates the antimicrobial and antibiofilm activity of AF and its two derivatives in which the thiosugar ligand is replaced by acetylcysteine (AF-AcCys) or naproxen (AF-Napx), against and . : AF was conjugated by transmetalation with either naproxen or acetylcysteine. Assessments of their stability in DMSO/HO and lipophilicity expressed as the LogP were performed. The antimicrobial activity of AF and its analogues were investigated by broth microdilution assay to determine the minimum inhibitory concentration (MIC) and versus biofilm to obtain the minimum bactericidal biofilm concentration (MBBC) and minimum biofilm eradication concentration (MBEC). : AF derivatives were found to be stable in a DMSO/HO mixture for 48 h. AF-Napx showed a LogP = 1.25 ± 0.22, close to AF, while AF-AcCys had a LogP = -0.95. MIC values of and were ranging from 2 µM to 0.25 µM, and ≤0.12 µM, respectively. Both AF and AF-Napx maintained efficacy against biofilm-embedded and at non-cytotoxic concentrations, with AF-Napx demonstrating lower MBBC values for . : AF, and especially its naproxen conjugate, holds potential as a therapeutic agent for treating biofilm-associated infections caused by and , particularly in device-related infections where both infection and inflammation are present.