NOVEL ANTIMUTAGENIC COMPOUNDS

新型抗突变化合物

• 批准号: 3186005
• 负责人: Lester A. Mitscher
• 金额: $ 19.49万
• 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/3186005
• 关键词: Salmonella; aging; alkylating agents; cancer prevention; carcinogenesis; chemical structure function; drug screening /evaluation; environmental health; gene induction /repression; 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.

我们已经对自然发生的小说进行了研究 抗原剂。 反植物是个体化学物质 减少自发或损伤数量的化合物 - 诱导完整细胞群体的突变。 该建议是 使用短期测试进行筛选；通过使用生物测定 定向方法；通过光谱确定化学结构 和湿化学方法论；确定结构活性 系统合成和化学转化的关系； 探索生物学特性；并探索分子 自然起源的新型反植物的作用机理。 这 长期目标是使潜在的化学预防剂 反对遗传损害，也许是癌症。 使用专门为此目的开发的生物测定法，Glycyrrhiza Glabra，一种自古代以来人类使用的众所周知的植物 它的调味和药用特性被证明是 可重现活动。 该活动存在于酚类 分数以及色谱分辨率后，类黄酮 发现毛ren烯，在较小程度上发现了glabridin和glabrol， 成为活跃成分。 生产这些的生物测定 这项试验研究的成功结果基于众所周知的 AMES短期沙门氏菌诱变分析，但通过 使用烷基化剂（甲基磺酸乙酯）诱导 突变。 基于此成功，建议使用屏幕 还包括其他诱变处理，以筛选 相关天然抗抗原物质的其他例子 植物并确定活性成分。 一个程序 提出了伴随着生物验化的化学修饰 以系统的方式探索结构之间的关系 和这些新型系列的活动。 除了对诱变现象的见解和 据信诱变性发挥的其他生物学领域 重要作用（衰老，遗传，致癌性， 环境问题）这些化合物可能具有一定的潜力 预防性人类医学。