NEW TRITERPENOIDS FROM INDIAN PLANTS TO PREVENT CANCER

NIH Grant R01 CA78814-01A1的主要目标是开发称为三萜类化合物的新化学制剂，用于癌症的化学预防。从世界范围内常见癌症的高死亡率可以很容易地看出需要新的药物来预防癌症。在达特茅斯医学院药理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。到目前为止，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。研究策略一直是让化学家合成新的三萜类化合物，然后让生物学家评估这些新化合物的有用药理活性。我们现在希望在高度相关的国际合作中推广这一方法，让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进来。拟议的合作是以达特茅斯项目为蓝本的。对于用于药物开发的新的三萜结构有很大的需求。达特茅斯项目在获取三萜类化合物方面受到限制，三萜类化合物以天然产物的形式出现在亚洲广泛分布的植物中。班加罗尔科学研究所的化学系在分离和鉴定印度本土植物中发现的许多三萜类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)它们本身将作为潜在的药理学试剂进行测试；2)它们将被用作合成将在该计划中测试的新药的起点，方式类似于达特茅斯计划。此外，班加罗尔研究所分子生殖、发育和遗传学系在基本分子和细胞生物学方面拥有出色的技能，该系的研究人员也将在该项目的生物学方面进行合作，同样是以类似于达特茅斯计划的方式。这一拟议项目的基本特点将是班加罗尔和达特茅斯的调查人员之间的密切合作和信息和材料的交流。将在班加罗尔进行的化学和生物课程的性质是，它将扩大和加强达特茅斯项目的努力，而不是与其重复或重叠。

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.