NEW TRITERPENOIDS FROM INDIAN PLANTS TO PREVENT CANCER

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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.