ADVANCES IN SELENIUM SUPPLEMENTATION

补硒方面的进展

• 批准号: 6129418
• 负责人: JEANETTE C ROBERTS
• 金额: $ 10.82万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-06-01 至 2002-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6129418
• 关键词: blood chemistry; chemoprevention; cysteine; cytotoxicity; dietary aminoacid; dietary supplements; disease /disorder model; drug delivery systems; drug design /synthesis /production; drug screening /evaluation; enzyme activity; enzyme induction /repression; glutathione peroxidase; laboratory mouse; lung neoplasms; neoplasm /cancer nutrition therapy; nitrosamines; nonhuman therapy evaluation; nutrition related tag; pharmacokinetics; prodrugs; selenated sulfur aminoacid; selenium; tissue /cell culture

This project proposes the preparation and preliminary studies of selenazoidine carboxylic acids as novel selenium delivery agents. Selenium is of growing importance in human health beyond its well-recognized role as a micronutrient. For example, selenium has exhibited exciting activity as a cancer chemopreventive agent against disease in several organs, caused by a variety of carcinogens. Selenium is also known for its toxicity, however, making the development of clinically valuable agents a distinct challenge that must be accomplished with extreme care and creativity. The selenocysteine and were designed to provide a continuous supply of the amino acid over time at levels high and sustained enough to have therapeutic value but not high enough to produce toxicity. The current application will accomplish two specific aims: (1) synthesizing two prototype selenazolidine prodrugs; and (2) conducting pilot studies in a mouse model to explore: (a) the toxicity of the novel agents; (b) their effect on the selenium content in blood and tissue; (c) their ability to provide biologically available selenium as measured by increased activity of the selenium-dependent enzyme, glutathione peroxidase; and (d) their ability to function as chemopreventive agents against nitrosamine-induced lung cancer. These analogs are completely novel. It appears to be an entirely new approach in the selenium field and may allow the potential of selenium as a preventive and/or therapeutic agent in human disease to be clinically realized.

本项目提出硒代啶的制备及初步研究 羧酸作为新型硒输送剂。硒正在生长 它对人类健康的重要性超出了其作为微量营养素的公认作用。 例如，硒作为癌症化学预防剂表现出令人兴奋的活性 对抗由多种致癌物引起的多种器官疾病的药剂。 硒也因其毒性而闻名，然而，这使得临床上硒的开发 有价值的代理人是一个必须极其小心地完成的独特挑战 和创造力。硒代半胱氨酸旨在提供持续供应 随着时间的推移，氨基酸的水平保持在足够高的水平，足以具有治疗作用 值但不足以产生毒性。当前的应用程序将完成 两个具体目标： (1)合成两种原型硒唑烷前药； (2) 进行 在小鼠模型中进行的初步研究旨在探索：(a) 该小说的毒性 代理； (b) 它们对血液和组织中硒含量的影响； (c) 他们的 提供生物可用硒的能力（通过增加来衡量） 硒依赖性酶谷胱甘肽过氧化物酶的活性；和（四） 它们作为针对亚硝胺诱导的化学预防剂的能力 肺癌。 这些类似物是完全新颖的。它似乎完全是一个 硒领域的新方法，可能会发挥硒作为 人类疾病的预防和/或治疗剂在临床上得以实现。