Mikolasch Annett, Niedermeyer Timo Horst Johannes, Lalk Michael, Witt Sabine, Seefeldt Simone, Hammer Elke, Schauer Frieder, Gesell Salazar Manuela, Hessel Susanne, Jülich Wolf-Dieter, Lindequist Ulrike
Institute of Microbiology, Ernst-Moritz-Arndt-University Greifswald, Greifswald, Germany.
Chem Pharm Bull (Tokyo). 2007 Mar;55(3):412-6. doi: 10.1248/cpb.55.412.
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.
通过使用来自栓菌属或嗜热毁丝霉的漆酶，将2,5-二羟基苯甲酸衍生物与氨基头孢菌素头孢羟氨苄、头孢氨苄、头孢克洛以及结构相关的碳青霉烯类氯碳头孢进行胺化反应，合成了16种新型头孢菌素。在琼脂扩散试验中，所有产物均抑制了几种革兰氏阳性细菌菌株的生长，其中包括耐甲氧西林金黄色葡萄球菌和耐万古霉素肠球菌。这些产物保护小鼠免受对对照动物致死的金黄色葡萄球菌感染。新化合物的细胞毒性和急性毒性可忽略不计。结果表明漆酶在合成潜在新型抗生素方面的有用性。新化合物的生物活性刺激了进一步的药理试验。
