Augustyns K, Amssoms K, Yamani A, Rajan P K, Haemers A
Department of Medicinal Chemistry, University of Antwerp (UIA), Universiteitsplein, Los Antwerpen, B-2610, Belgium.
Curr Pharm Des. 2001 Aug;7(12):1117-41. doi: 10.2174/1381612013397564.
Trypanothione is the key molecule in the defence mechanism of Trypanosoma and Leishmania against oxidative stress. The uniqueness of trypanothione makes the metabolism of this molecule an attractive target in antitrypanosomal and antileishmanial drug design. It became clear that this antioxidant cascade can be considered as the "Achilles heel" of these parasites. The following targets and their respective inhibitors will be discussed: biosynthesis of trypanothione with glutathionylspermidine synthetase and trypanothione synthetase; biosynthesis of glutathione with gamma-glutamylcysteine synthetase; biosynthesis of spermidine with ornithine decarboxylase; trypanothione hydroperoxide metabolism with tryparedoxine peroxidase, tryparedoxine and trypanothione reductase.
锥虫硫醇是锥虫和利什曼原虫抵御氧化应激防御机制中的关键分子。锥虫硫醇的独特性使得该分子的代谢成为抗锥虫和抗利什曼原虫药物设计中一个有吸引力的靶点。很明显，这种抗氧化级联反应可被视为这些寄生虫的“阿喀琉斯之踵”。将讨论以下靶点及其各自的抑制剂：由谷胱甘肽亚精胺合成酶和锥虫硫醇合成酶参与的锥虫硫醇生物合成；由γ-谷氨酰半胱氨酸合成酶参与的谷胱甘肽生物合成；由鸟氨酸脱羧酶参与的亚精胺生物合成；由锥虫硫氧还蛋白过氧化物酶、锥虫硫氧还蛋白和锥虫硫醇还原酶参与的锥虫硫醇过氧化氢代谢。
