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

摘要

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 mug/mL, MBC=7.8 mug/mL) and 22 (MIC=1.95 mug/mL, MBC=7.8 mug/mL) was significantly greater than that of the lead compounds, 1-3 and reference antibiotics penicillin G (MIC=31.25 mug/mL) and ciprofloxacin (MIC=7.8 mug/mL) and comparable to that of vancomycin (MIC=0.97 mug/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.