Hamilton Chris J, Saravanamuthu Ahilan, Fairlamb Alan H, Eggleston Ian M
Division of Biological Chemistry & Molecular Microbiology, Faculty of Life Sciences, Carnelley Building, University of Dundee, DD1 4HN, Dundee, UK.
Bioorg Med Chem. 2003 Aug 15;11(17):3683-93. doi: 10.1016/s0968-0896(03)00344-4.
The synthesis and evaluation of 3,5-disubstituted benzofuran derivatives as time-dependent inhibitors of the protozoan oxidoreductase trypanothione reductase are reported. These molecules were designed as simplified mimetics of the naturally occurring spermidine-bridged macrocyclic alkaloid lunarine 1, a known time-dependent inhibitor of trypanothione reductase. In this series of compounds the bis-polyaminoacrylamide derivatives 2-4 were all shown to be competitive inhibitors, but only the bis-4-methyl-piperazin-1-yl-propylacrylamide derivative 4 displayed time-dependent activity. The kinetics of time dependent inactivation of trypanothione reductase by 1 and 4 have been determined and are compared and discussed herein.
报道了3,5-二取代苯并呋喃衍生物作为原生动物氧化还原酶锥虫硫醇还原酶的时间依赖性抑制剂的合成与评价。这些分子被设计为天然存在的亚精胺桥连大环生物碱鲁那灵1的简化模拟物，鲁那灵1是一种已知的锥虫硫醇还原酶的时间依赖性抑制剂。在这一系列化合物中，双聚氨基丙烯酰胺衍生物2-4均显示为竞争性抑制剂，但只有双-4-甲基-哌嗪-1-基-丙基丙烯酰胺衍生物4表现出时间依赖性活性。已测定了1和4对锥虫硫醇还原酶的时间依赖性失活动力学，并在此进行了比较和讨论。
