NEW TRITERPENOIDS FROM INDIAN PLANTS TO PREVENT CANCER

美国国立卫生研究院拨款R01 CA78814-01A1的主要目标是开发新的化学制剂，称为三萜，用于化学预防癌症。从世界范围内常见形式的癌症的持续高死亡率不难看出，需要新的药物来预防癌症。在达特茅斯医学院药学系和达特茅斯学院化学系的共同努力下，我们已经在这方面取得了很好的进展。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。研究策略是化学家合成新的三萜，然后生物学家评估这些新化合物的有用药理活性。我们现在希望在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参与的高度相关的国际合作中推广同样的方法。拟议中的合作是以达特茅斯学院的项目为蓝本的。目前迫切需要新的三萜结构用于药物开发。达特茅斯项目在获取三萜方面受到限制，三萜是在亚洲广泛存在的植物中作为天然产物存在的。班加罗尔科学研究所化学系在分离和描述印度本土植物中发现的许多三萜化合物方面有着杰出的出版记录。这些药物将在班加罗尔用于两个目的：1)它们将作为潜在的药理学药物进行测试；2)它们将被用作合成新药的起点，这些新药将在本项目中进行测试，其方式与达特茅斯项目类似。此外，班加罗尔研究所的分子繁殖、发育和遗传学部门在基本分子和细胞生物学方面有出色的技能，该部门的研究人员也将在这个项目的生物学方面进行合作，方式与达特茅斯项目类似。这个拟议项目的基本特点将是班加罗尔的研究人员与达特茅斯的研究人员之间的密切合作和交换资料和材料。将在班加罗尔进行的化学和生物学的性质将是这样的，它将扩大和加强达特茅斯项目的努力，而不会与之重复或重叠。

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.