Novel Cephalosporins Synthesized by Amination of 2,5-Dihydroxybenzoic Acid Derivatives Using Fungal Laccases 2

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  • Novel Cephalosporins Synthesized by Amination of 2,5-Dihydroxybenzoic Acid Derivatives Using Fungal Laccases II

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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.

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