title: Novel cephalosporins synthesized by amination of 2,5-dihydroxybenzoic acid derivatives using fungal laccases II.
abstract: 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.
authors.affiliation: Institute of Microbiology, Ernst-Moritz-Arndt-University Greifswald, Greifswald, Germany. annett.mikolasch@gmx.de
authors.forename: Annett
authors.initials: A
authors.lastname: Mikolasch
authors.forename: Timo Horst Johannes
authors.initials: TH
authors.lastname: Niedermeyer
authors.forename: Michael
authors.initials: M
authors.lastname: Lalk
authors.forename: Sabine
authors.initials: S
authors.lastname: Witt
authors.forename: Simone
authors.initials: S
authors.lastname: Seefeldt
authors.forename: Elke
authors.initials: E
authors.lastname: Hammer
authors.forename: Frieder
authors.initials: F
authors.lastname: Schauer
authors.forename: Manuela
authors.initials: M
authors.lastname: Gesell Salazar
authors.forename: Susanne
authors.initials: S
authors.lastname: Hessel
authors.forename: Wolf-Dieter
authors.initials: WD
authors.lastname: Jülich
authors.forename: Ulrike
authors.initials: U
authors.lastname: Lindequist
mesh_terms: 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
chemical_list: D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D005841:Gentisates; D007166:Immunosuppressive Agents; D003520:Cyclophosphamide; D042845:Laccase; C010925:2,5-dihydroxybenzoic acid