The synthesis of phenylalanine-derived C5-substituted rhodanines and their activity against selected methicillin-resistant Staphylococcus aureus (MRSA) strains

A series of rhodanine compounds containing various substituents at the N3- and C5-positions were synthesized and their in vitro activity against a panel of clinically relevant MRSA strains was determined. The anti-MRSA activity of compounds 21 (MIC = 3.9 mu g/mL, MBC = 7.8 mu g/mL) and 22 (MIC = 1.95 mu g/mL, MBC = 7.8 mu g/mL) was significantly greater than that of the lead compounds, 1-3 and reference antibiotics penicillin G (MIC = 31.25 mu g/mL) and ciprofloxacin (MIC = 7.8 mu g/mL) and comparable to that of vancomycin (MIC = 0.97 mu g/mL). Compounds 21 and 22 were found to be bactericidal at only 2-4-fold higher than their MIC concentrations. In addition, their MIC values remained unchanged in the presence or absence of 10% serum. Overall, the results suggest that compounds 21 and 22 may be of potential use in the treatment of MRSA infections. (C) 2010 Elsevier Masson SAS. All rights reserved.