Novel cephalosporins synthesized by amination of 2,5-dihydroxybenzoic acid derivatives using fungal laccases II.
Sixteen novel cephalosporins were synthesized by amination of 2,5-dihydroxybenzoic acid derivatives with the aminocephalosporins cefadroxil, cefalexin, cefaclor, and the structurally related carbacephem loracarbef using laccases from Trametes sp. or Myceliophthora thermophila. All products inhibited the growth of several Gram positive bacterial strains in the agar diffusion assay, among them methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci. The products protected mice against an infection with Staphylococcus aureus lethal to the control animals. Cytotoxicity and acute toxicity of the new compounds were negligible. The results show the usefulness of laccase for the synthesis of potential new antibiotics. The biological activity of the new compounds stimulates intensified pharmacological tests.
Mikolasch
Annett
A
Institute of Microbiology, Ernst-Moritz-Arndt-University Greifswald, Greifswald, Germany. annett.mikolasch@gmx.de
Niedermeyer
Timo Horst Johannes
TH
Lalk
Michael
M
Witt
Sabine
S
Seefeldt
Simone
S
Hammer
Elke
E
Schauer
Frieder
F
Gesell Salazar
Manuela
M
Hessel
Susanne
S
Jülich
Wolf-Dieter
WD
Lindequist
Ulrike
U
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects; D002511:Cephalosporins / Q000138:chemical synthesis*; D003520:Cyclophosphamide; D024901:Drug Resistance, Multiple, Bacterial; D005260:Female; D005658:Fungi / Q000201:enzymology*; D005841:Gentisates / Q000737:chemistry*; D016867:Immunocompromised Host; D007166:Immunosuppressive Agents; D042845:Laccase / Q000737:chemistry / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D013203:Staphylococcal Infections / Q000188:drug therapy
D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D005841:Gentisates; D007166:Immunosuppressive Agents; D003520:Cyclophosphamide; D042845:Laccase; C010925:2,5-dihydroxybenzoic acid