Technische Universität Braunschweig, Institut für Pharmazeutische Chemie, Beethovenstrasse 55, D-38106 Braunschweig, Germany.
Eur J Med Chem. 2010 Jan;45(1):335-42. doi: 10.1016/j.ejmech.2009.10.018. Epub 2009 Oct 14.
A collection of paullones was tested for inhibitory activity against mitochondrial malate dehydrogenase (mMDH) as a biological target for antiproliferative activity. Based on the results of this screening, 5-benzylpaullones and paullone-9-carboxylic acid alkyl esters were developed as selective mMDH inhibitors. The new derivatives did not show noteworthy antiproliferative activity when tested on a panel of cancer cell lines, suggesting that mMDH inhibition is of minor relevance for the growth inhibition caused by paullones.
为了寻找有抗增殖活性的生物靶标，我们对一系列的paullones 进行了抑制线粒体苹果酸脱氢酶（mMDH）活性的筛选。基于筛选结果，5-苄基paullones 和 paullone-9-羧酸烷基酯被开发为选择性的 mMDH 抑制剂。这些新衍生物在一组癌细胞系中的测试并未显示出显著的抗增殖活性，这表明 mMDH 的抑制对于 paullones 引起的细胞生长抑制的相关性不大。
