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

Graphical abstractThe anti-MRSA activity of the phenylalanine-derived rhodanine analogs 21 (MIC = 3.9 μg/mL, MBC = 7.8 μg/mL) and 22 (MIC = 1.95 μg/mL, MBC = 7.8 μg/mL) was found to be comparable to the reference antibiotic vancomycin (MIC = 0.97 μg/mL).Figure optionsDownload full-size imageDownload as PowerPoint slide