Taxol, a complex diterpene structure isolated from yew tress and, more recently, yew plant cell cultures shows strong potential as treatment for a number of cancers. A second generation version of this drug has yet to be found which is more effective, has fewer side effects, can be more easily formulated, administered, etc. The proposed work is designed to discover lead candidates for such a second generation anti-cancer drug. Rather than the more traditional approach of organic synthesis, this plan uses the potential for plant cell cultures to provide a wide diversity of taxol-like compounds (taxanes). Both cell lines which are currently producing taxol and cell lines selected specifically to enhance diverse taxane production will be used to generate mixtures of new compounds. These mixtures will then be separated and prescreened using carcinoma cytotoxicity, tubulin binding assay and a series of micro analytical chemical procedures. Candidates will be isolated, full structures determined and submitted for cytotoxicity profile characterization to the National Cancer Institute.
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