Diwischek Florian, Morschhäuser Joachim, Holzgrabe Ulrike
Institut für Pharmazie und Lebensmittelchemie, Universität Würzburg, Würzburg, Germany.
Arch Pharm (Weinheim). 2009 Mar;342(3):150-64. doi: 10.1002/ardp.200800160.
Overexpression of the ABC transporters Cdr1 and Cdr2 or the major facilitator Mdr1 causes multidrug resistance in the human fungal pathogen Candida albicans. The fatty acid synthesis inhibitor cerulenin and the structurally unrelated Golgi transport inhibitor brefeldin A are substrates for both types of efflux pumps in Candida albicans. In an effort to overcome efflux pump-mediated drug resistance in Candida albicans, cerulenin analogues were generated using a variety of synthesis pathways. The so obtained cerulenin derivatives were tested on multidrug-resistant Candida albicans isolates which constitutively overexpress either Mdr1 or Cdr1 and Cdr2. Some of these compounds were found to decrease Mdr1-mediated resistance to brefeldin A up to eightfold compared to the control.
ABC转运蛋白Cdr1和Cdr2或主要易化子Mdr1的过表达会导致人类真菌病原体白色念珠菌产生多药耐药性。脂肪酸合成抑制剂浅蓝菌素和结构不相关的高尔基体转运抑制剂布雷菲德菌素A是白色念珠菌中两种类型外排泵的底物。为了克服白色念珠菌中外排泵介导的耐药性，通过多种合成途径生成了浅蓝菌素类似物。将如此获得的浅蓝菌素衍生物用于对组成型过表达Mdr1或Cdr1和Cdr2的多药耐药白色念珠菌分离株进行测试。与对照相比，发现其中一些化合物可将Mdr1介导的对布雷菲德菌素A的耐药性降低多达八倍。
