8-Acyloxy-1,3-benzoxazine-2,4-diones as siderophore components for antibiotics.
8-Acyloxy-1,3-benzoxazine-2,4-diones as masked catechol derivatives represent a novel type of siderophore components, whose growth promoting activity is low or not existing if tested alone. But after conjugation with beta-lactam antibiotics the resulting conjugates show a significantly increased antibacterial activity against Gram-negative bacteria compared with their parent antibiotics. Investigations using a set of penetration and iron transport mutants demonstrated that the conjugates use iron transport systems to penetrate the bacterial outer membrane. Title compounds were synthesized from (2,3-dimethoxycarbonyloxy)-benzoic acid and different amino compounds. Conjugates with penicillins and cephalosporins were prepared.
Wittmann
S
S
Department of Biostructure Chemistry, Hans-Knöll-Institute for Natural Product Research, Jena, Germany.
Scherlitz-Hofmann
I
I
Möllmann
U
U
Ankel-Fuchs
D
D
Heinisch
L
L
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects; D002463:Cell Membrane Permeability / Q000187:drug effects; D004926:Escherichia coli / Q000187:drug effects; D007094:Imides / Q000138:chemical synthesis* / Q000494:pharmacology; D007769:Lactams; D008826:Microbial Sensitivity Tests; D010078:Oxazines / Q000138:chemical synthesis* / Q000494:pharmacology; D021281:Quantitative Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D007094:Imides; D007769:Lactams; D010078:Oxazines