NOVEL ANTIMUTAGENIC COMPOUNDS

新型抗突变化合物

• 批准号: 3186003
• 负责人: Lester A. Mitscher
• 金额: $ 20.36万
• 依托单位: UNIVERSITY OF KANSAS LAWRENCE
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-04-01 至 1992-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3186003
• 关键词: Salmonella; aging; alkylating agents; cancer prevention; carcinogenesis; chemical structure function; drug screening /evaluation; environmental health; medicinal plants; methane sulfonate; mutagen testing; neoplasm /cancer genetics; plant extracts; preneoplastic state

We have undertaken a study of novel naturally occuring antimutagenic agents. Antimutagens are individual chemical compounds that decrease the numbers of spontaneous or injury- induced mutations in intact cell populations. This proposal is to use short-term tests to screen for; isolate by use of bioassay directed methodology; determine chemical structure by spectroscopic and wet chemical methodology of; determine structure-activity relations by systematic syntheses and chemical transformations of; explore the biological properties of; and explore the molecular mechanisms of action of novel antimutagens of natural origin. The long-term objectives are to make potential chemopreventive agents against genetic damage and, perhaps, cancer. Using a bioassay specially developed for the purpose, Glycyrrhiza glabra, a well known plant used by humans since ancient times for its flavoring and medicinal properties, was shown to be reproducably active. The activity was present in the phenolic fractions and, after chromatographic resolution, the flavanoids glabrene and, to a lesser extent, glabridin and glabrol, were found to be the active constituents. The bioassay which produced these successful results in this trial study is based upon the well known Ames short-term Salmonella mutagenicity assay but modified through the use of an alkylating agent (ethyl methanesulfonate) to induce mutations. Based upon this success, it is proposed to use the screen, with the inclusion of other mutagenic treatments as well, to screen for additional examples of natural antimutagenic substances in related plants and to identify the active constituents. A program of chemical modification accompanied by biotesting is proposed so as to explore in a systematic way the relationship between structure and activity in these novel series. In addition to the insights into the mutagenic phenomenon and the other biological areas where mutagenicity is believed to play an important role (ageing, heredity, carcinogenicity, environmental concerns) these compounds may have some potential in preventive human medicine.

我们对自然发生的小说进行了研究 抗突变剂。 抗突变剂是单独的化学物质 减少自发或损伤的数量的化合物- 在完整的细胞群体中诱导突变。 这项建议是为了 用短期试验筛选;用生物测定法分离 定向方法学;用光谱测定化学结构 和湿化学方法;测定结构活性 通过系统合成和化学转化的关系; 探索的生物特性;并探索分子 天然来源的新型抗突变剂的作用机制。 的 长期目标是使潜在的化学预防剂 对抗基因损伤，也许还有癌症 使用专门为此目的开发的生物测定法， glabra，自古以来人类使用的一种众所周知的植物， 它的调味和药用特性，被证明是 可再生的活性。 活性存在于酚类化合物中， 馏分和色谱分离后，黄酮类化合物 光甘草烯，以及在较小程度上，光甘草定和光甘草醇，被发现， 是有效成分。 产生这些的生物测定 这项试验研究的成功结果是基于众所周知的 艾姆斯短期沙门氏菌致突变试验，但通过以下方法进行了修改： 使用烷基化剂（甲磺酸乙酯）诱导 突变。 基于这一成功，建议使用屏幕， 包括其他诱变处理，以筛选 天然抗突变物质的其它实例 植物和鉴定活性成分。 的程序 提出了伴随生物测试的化学改性， 系统地探讨结构与 在这些小说系列中。 除了对诱变现象的了解和 其他生物领域，诱变性被认为是发挥作用， 重要作用（衰老、遗传、致癌性， 这些化合物可能具有一定的潜力， 人类预防医学