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SELENIUM METABOLISM AND ANTICARCINOGENIC ACTION

硒的代谢和抗癌作用

基本信息

批准号：
6269293
负责人：
HOWARD GANTHER
金额：
$ 17.1万
依托单位：
ROSWELL PARK CANCER INSTITUTE
依托单位国家：
美国
项目类别：
财政年份：
1998
资助国家：
美国
起止时间：
1998-03-01 至 1999-02-18
项目状态：
已结题

项目摘要

The identification of novel selenium compounds that have good chemopreventive activity and low toxicity is of great potential benefit. We have uncovered important determinants of these effects that resulted in the discovery of a new class of chemopreventive compounds. These compounds provide a means for relatively straightforward exploration of mechanisms of chemopreventive action compared to other organoselenium compounds that show less metabolic stability. It is proposed that lipophilic derivatives of selenium and sulfur are produced through known biochemical reactions to create similar types of chemopreventive compounds. The purpose of this study is to synthesize novel organoselenium compounds for testing, study their metabolism in the whole animal to correlate critical metabolites with chemopreventive activity, and define the biochemical origin of critical metabolites in cell-free systems. The long-term goal is to develop improved chemopreventive compounds of low toxicity for possible long-term use in humans. This work will lead to a better understanding of chemopreventive mechanisms of selenium. It also provides an important conceptual advance in understanding how chemopreventive activity can be developed and enhanced during the metabolism of selenium or sulfur in plants and animals.

具有良好生物活性的新型硒化合物的鉴定化学预防活性和低毒性具有巨大的潜在益处。我们已经发现了这些影响的重要决定因素，发现了一类新的化学预防化合物。这些化合物提供了一种相对简单的探索方法，与其他有机硒相比的化学预防作用机制代谢稳定性较差的化合物。拟将硒和硫的亲脂性衍生物通过已知的方法制备，产生类似的化学预防作用化合物. 本研究的目的是合成新的对有机硒化合物进行检测，研究其在整体代谢中的作用动物将关键代谢物与化学预防活性相关联，并确定无细胞代谢中关键代谢物的生化来源系统. 长期目标是开发改进的化学预防低毒性化合物，可长期用于人类。这项工作将有助于更好地了解化学预防机制，硒。它还提供了一个重要的概念进步，了解如何开发和增强化学预防活性在植物和动物体内硒或硫的代谢过程中。