Improvement of water-soluble cephalosporin derivatives having antibacterial activity against methicillin-resistant Staphylococcus aureus.
We evaluated a series of novel cephem antibiotics, N-alkylpyridinium (alkyl group), N-carboxyethylpyridinium (carboxylic group), N-sulfoethylpyridinium (sulfonic group) and N-alkylquaternary ammonium salts (ammonioethyl group), N-alkyl-aromatic-quaternary ammonium salts and N-alkyl-heterocyclic quaternary ammonium salts (cyclic group) as vinylthio pyridinium derivatives at the C-3 position and hydroxyiminoaminothiazol at the C-7 position, for their activity against methicillin-resistant Staphylococcus aureus (MRSA) and their solubility, by measuring the minimum inhibitory concentrations (MICs) and the dissolving test in phosphate buffer. All tested compounds, except for the alkyl group, showed good solubility (>10%) in 1/15 M phosphate buffer (pH 7.2). The concentrations required to inhibit 80% of the bacterial strains (MIC80s) of the alkyl group, carboxylic group, sulfonic group, ammonioethyl group and cyclic group against MRSA were 1.56, 12.5-25, 6.25, 1.56 and 1.56 microg/ml, respectively. These results indicated that the ammonioethyl and cyclic groups yield the maximum anti-MRSA and anti-Enterococcus faecalis activity, and also good water solubility.
Hanaki
H
H
Department of Bacteriology, School of Medicine, Juntendo University, Tokyo, Japan. hanaki@med.juntendo.ac.jp
Nomura
S
S
Akagi
H
H
Hiramatsu
K
K
D002511:Cephalosporins / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006863:Hydrogen-Ion Concentration; D016106:Methicillin Resistance; D008826:Microbial Sensitivity Tests; D012995:Solubility; D013203:Staphylococcal Infections / Q000188:drug therapy*; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000472:pathogenicity
D002511:Cephalosporins