Cerulenin Analogues as Inhibitors of Efflux Pumps in Drug-resistant<i>Candida albicans</i>
作者:Florian Diwischek、Joachim Morschhäuser、Ulrike Holzgrabe
DOI:10.1002/ardp.200800160
日期:2009.3
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
ABC 转运蛋白 Cdr1 和 Cdr2 或主要促进因子 Mdr1 的过度表达会导致人类真菌病原体白色念珠菌的多药耐药。脂肪酸合成抑制剂 cerulenin 和结构无关的高尔基体转运抑制剂 brefeldin A 是白色念珠菌中两种类型的外排泵的底物。为了克服白色念珠菌中外排泵介导的耐药性,使用多种合成途径产生了蓝蓝素类似物。对如此获得的蓝藻素衍生物进行了多重耐药性白色念珠菌分离株的测试,这些分离株组成性地过度表达 Mdr1 或 Cdr1 和 Cdr2。与对照相比,发现其中一些化合物可将 Mdr1 介导的对布雷菲尔德菌素 A 的抗性降低多达八倍。