Minimum essential structural requirements for lactam antibiotic action.
A mechanism of action encompassing mono- and bicyclic beta-lactams has been proposed previously, which stresses the importance of formation of an electron transfer (ET) entity (conjugated iminium) as a requirement for antibiotic activity, in association with enzyme inactivation. Additional evidence in support of this contention is now provided. Reduction potentials for several cephalosporins and pyrazolidinones, all of which contain an oximino functionality in the side chain, were observed in the range of -0.6 to -0.7 V. Comparison is made with related compounds lacking imine. Agents containing side chain hydrazone, oxamazins (mono beta-lactams), and lactivicin are discussed based on the ET approach.
Kovacic
P
P
Department of Chemistry, University of Wisconsin, Milwaukee 53201.
Ames
J R
JR
Ryan
M D
MD
D000900:Anti-Bacterial Agents / Q000032:analysis / Q000494:pharmacology*; D001643:Bridged Bicyclo Compounds / Q000032:analysis / Q000494:pharmacology; D004563:Electrochemistry; D004579:Electron Transport; D007769:Lactams; D008968:Molecular Conformation; D010455:Peptides; D010456:Peptides, Cyclic / Q000032:analysis / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D001643:Bridged Bicyclo Compounds; D007769:Lactams; D010455:Peptides; D010456:Peptides, Cyclic; C051231:lactivicin