Garrard E A, Borman E C, Cook B N, Pike E J, Alberg D G
Department of Chemistry, Carleton College, Northfield, Minnesota 55057, USA.
Org Lett. 2000 Nov 16;2(23):3639-42. doi: 10.1021/ol0065423.
Trypanothione reductase (TR) catalyzes the NAPDH-dependent reduction of the spermidine-glutathione conjugate trypanothione, an antioxidant found in Trypanosomatid parasites. TR plays an essential role in the parasite's defense against oxidative stress and has emerged as a prime target for drug development. Here we report the synthesis of several trypanothione analogues and their inhibitory effects on T. cruzi TR. All are competitive inhibitors with K(i) values ranging from 30 to 91 microM.
锥虫硫醇还原酶（TR）催化依赖于烟酰胺腺嘌呤二核苷酸磷酸（NAPDH）的亚精胺 - 谷胱甘肽共轭物锥虫硫醇的还原反应，锥虫硫醇是一种在锥虫属寄生虫中发现的抗氧化剂。TR在寄生虫抵御氧化应激中起着至关重要的作用，并且已成为药物开发的主要靶点。在此我们报告了几种锥虫硫醇类似物的合成及其对克氏锥虫TR的抑制作用。所有这些都是竞争性抑制剂，其抑制常数（K(i)）值范围为30至91微摩尔。
