NEW TRITERPENOIDS FROM INDIAN PLANTS TO PREVENT CANCER

来自印度植物的新三萜类化合物可预防癌症

• 批准号: 6394987
• 负责人: Michael B Sporn
• 金额: $ 4.03万
• 依托单位: DARTMOUTH COLLEGE
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-01 至 2003-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6394987
• 关键词: India; cancer prevention; cell differentiation; chemical kinetics; chemical structure; chemical synthesis; chemoprevention; cooperative study; enzyme activity; enzyme induction /repression; enzyme inhibitors; genetic promoter element; genetic transcription; laboratory mouse; neoplasm /cancer pharmacology; neoplastic cell; nitric oxide synthase; pharmacokinetics; plant extracts; prostaglandin endoperoxide synthase; terpenes; tissue /cell culture

The primary goal of NIH Grant R01 CA78814-01A1 is to develop new chemical agents, called triterpenoids, for the chemoprevention of cancer. The need for new agents to prevent cancer is readily evident from the continuing worldwide high mortality rates for the common forms of cancer. In a collaborative effort between the Department of Pharmacology, Dartmouth Medical School, and the Department of Chemistry, Dartmouth College, we have already made excellent progress toward this. The project thus far has involved the joint efforts of molecular and cell biologists and organic chemists. The research strategy has been for the chemists to synthesize new triterpenoids, and then for the biologists to evaluate these new compounds for useful pharmacological activity. We now wish to extend this same approach in a highly related international collaboration, involving skilled biologists and chemists at the world-renowned Indian Institute of Science, in Bangalore, India. The proposed collaboration is modelled on the Dartmouth project. There is a major need for new triterpenoid structures to be used for drug development. The Dartmouth project is limited in its access to triterpenoids that occur as natural products in plants that are found widely in Asia. The Department of Chemistry at the Institute of Science in Bangalore has a distinguished publication record of isolating and characterizing many triterpenoids found in native Indian plants. Such agents will be used in Bangalore for two purposes: 1) they will be tested themselves as potential pharmacological agents; and 2) they will be used as a starting point for the synthesis of new drugs that will be tested in this program, in a manner similar to the Dartmouth program. Furthermore, there are excellent skills in basic molecular and cell biology in the Department of Molecular Reproduction, Development, and Genetics at the Institute in Bangalore, and investigators in that Department will also collaborate on the biological aspects of this project, again in a manner similar to the Dartmouth program. The essential feature of this proposed project will be a close collaboration and interchange of information and materials between the investigators in Bangalore and those at Dartmouth. The nature of the chemistry and biology that will be performed in Bangalore will be such that it will expand and enhance the efforts of the Dartmouth program, without duplicating or overlapping with it.

NIH Grant R01 CA78814-01A1的主要目标是开发新的化学剂（称为三萜），用于癌症的化学预防。 从持续的癌症形式的持续高死亡率中可以看出，新药物可以预防癌症的需求很明显。 在达特茅斯医学院的药理学系与达特茅斯学院化学系之间的合作努力中，我们已经取得了良好的进步。 迄今为止，该项目涉及分子和细胞生物学家以及有机化学家的共同努力。 该研究策略是为了使化学家合成新的三萜类化合物，然后生物学家评估这些新化合物以进行有用的药理活性。 现在，我们希望在高度相关的国际合作中扩展这种方法，涉及印度班加罗尔世界著名的印度科学研究所的熟练生物学家和化学家。 拟议的合作是在达特茅斯项目上建立的。 新三萜结构的主要需求用于药物开发。 达特茅斯（Dartmouth）项目的获取三萜类化合物的访问量是有限的，在亚洲广泛发现的植物中作为天然产品发生。 班加罗尔科学学院化学系的杰出出版记录是隔离和表征印度本地植物中许多三萜类化合物的表征。 此类药物将在班加罗尔使用两个目的：1）将其作为潜在的药理学剂进行测试； 2）它们将以与达特茅斯计划相似的方式将其作为合成新药物的合成起点。此外，班加罗尔研究所的分子繁殖，发展和遗传学系具有卓越的基本分子和细胞生物学技能，该部门的研究人员还将以类似于达特茅斯计划的方式就该项目的生物学方面进行合作。 该拟议项目的基本特征将是班加罗尔调查人员与达特茅斯研究人员之间的信息和材料的密切合作和互换。 在班加罗尔将进行的化学和生物学的性质将是这样，它将扩大和增强达特茅斯计划的努力，而不会重复或重叠。