Novel cephalosporins synthesized by amination of 2,5-dihydroxybenzoic acid derivatives using fungal laccases II

被引：48
|
作者：
Mikolasch, Annett
Niedermeyer, Timo Horst Johannes
Lalk, Michael
Witt, Sabine
Seefeldt, Simone
Hammer, Elke
Schauer, Frieder
Salazar, Manuela Gesell
Hessel, Susanne
Juelich, Wolf-Dieter
Lindequist, Ulrike
机构：
[1] Ernst Moritz Arndt Univ, Inst Microbiol, D-17489 Greifswald, Germany
[2] Ernst Moritz Arndt Univ, Inst Pharm, D-17489 Greifswald, Germany
[3] Ganomycin Soc Biomed Res Ltd, Greifswald, Germany
来源：
CHEMICAL & PHARMACEUTICAL BULLETIN | 2007年 / 55卷 / 03期
关键词：
cephalosporin; laccase; carbacephem; biotransformation; resistance;
D O I：
10.1248/cpb.55.412
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
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.
引用
收藏
页码：412 / 416
页数：5
相关论文
共 50 条
12345