ADVANCES IN SELENIUM SUPPLEMENTATION

超出提供的空间。本课题研究了新型硒载体材料--亚硒唑烷羧酸的制备及初步研究。除了公认的微量营养素的作用外，硒对人类健康的重要性也越来越大。例如，硒已显示出令人兴奋的活性，作为一种癌症化学防御剂，可以预防由多种致癌物引起的几个器官的疾病。然而，硒的毒性也是众所周知的，这使得开发具有临床价值的药物成为一个独特的挑战，必须以极端的谨慎和创造力来完成。这些硒代表L--硒半胱氨酸的“前药”形式。它们的设计目的是提供持续的氨基酸供应(作为硒的来源)，水平足够高和持续到足以具有治疗价值，但又不足以产生毒性。目前的应用将实现四个具体目标：(1)设计、合成和化学表征精选的新亚类硒唑烷前药的原型，以建立关键的结构-活性关系；(2)了解硒的化学/生化分解；(3)在已建立的A/J小鼠模型中进行动物研究，以研究新药物的毒性及其对基本生化参数的影响；(4)扩大动物研究范围：(A)调查新硒唑烷对烟草来源的肺癌致癌物的化学预防活性；(B)探索癌症化学预防的不同给药方案；(C)研究选定的硒与维生素E、维生素C或N-乙酰半胱氨酸(半胱氨酸来源)相结合以加强化学预防；以及(D)研究选定的硒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的方法，并可能使硒作为人类疾病预防和/或治疗剂的潜力在临床上实现。表演网站========================================Section End===========================================

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===========================================