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.
Hardej
Diane
D
Department of Pharmaceutical Sciences, College of Pharmacy and Allied Health Professions, St. John's University, 8000 Utopia Parkway, Jamaica, NY 11439, USA.
Ashby
Charles R
CR
Khadtare
Nikhil S
NS
Kulkarni
Shridhar S
SS
Singh
Satyakam
S
Talele
Tanaji T
TT
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D010649:Phenylalanine / Q000737:chemistry*; D012236:Rhodanine / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D010649:Phenylalanine; D012236:Rhodanine