ADVANCES IN SELENIUM SUPPLEMENTATION

超出所提供的空间。 本项目提出硒唑烷羧酸作为新型硒释放剂的制备和初步研究。硒在人类健康中的重要性越来越大，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，对由多种致癌物引起的多种器官疾病表现出令人兴奋的活性。然而，硒也因其毒性而闻名，这使得开发具有临床价值的药物成为一项独特的挑战，必须非常小心和创造性地完成。硒唑烷代表L-硒代半胱氨酸的“前药”形式.它们被设计为提供持续供应的氨基酸（作为硒的来源），其水平高且持续足以具有治疗价值，但不足以产生毒性。本申请将实现四个具体目标：（1）设计、合成和化学表征硒唑烷前药的新亚类的精心选择的原型，以允许开发关键的结构-活性关系;（2）理解硒唑烷的化学/生物化学分解;（3）在完善的A/J小鼠模型中进行动物研究，以研究新药剂的毒性以及它们对基本生化参数的影响;（4）将动物研究扩展到：（a）研究新硒唑烷对烟草衍生的肺癌原的癌症化学预防活性;（B）探索癌症化学预防的不同给药方案;（c）研究选择的硒唑烷与维生素E、维生素C或N-乙酰半胱氨酸的组合（d）研究所选硒唑烷在缺硒动物中的预防属性。 这些类似物是完全新颖的;它似乎是硒领域的一种全新方法，并且可以使硒作为人类疾病的预防和/或治疗剂的潜力在临床上得以实现。性能现场=

EXCEED THE SPACE PROVIDED. This project proposes the preparation and preliminary study of selenazolidine 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 selenazolidines represent "prodrug" forms of L- selenocysteine. They were designed to provide a continuous supply of the amino acid (as a source of selenium) at levels high and sustained enough to have therapeutic value but not high enough to produce toxicity. The current application will accomplish four specific aims: (1) Design, synthesize, and chemically characterize carefully selected prototypes of new subclasses of selenazolidine prodrugs to allow the development of critical structure-activity relationships; (2) Understand the chemical/biochemical breakdown of the selenazolidines; (3) Undertake animal studies in the well-established A/J mouse model to study toxicity of the novel agents, as well as their effect on basic biochemical parameters; (4) Expand animal studies to: (a) investigate the cancer chemopreventive activity of the new selenazolidines against a tobacco- derived lung carcinogen; (b) explore varied administration schedules for cancer chemoprevention; (c) study selected selenazolidines in combination with vitamin E, vitamin C, or N-acetylcysteine (cysteine source) to enhance chemoprevention; and (d) study the preventive attributes of selected selenazolidines in selenium-deficient animals. 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. PERFORMANCE SITE ========================================Section End===========================================