NATURALLY-OCCURRING ANTICANCER PRINCIPLES

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The search for new and effective treatments for the group of diseases known collectively as cancer continues to be a highly significant research goal. In continuance of a highly productive research program aimed at the several aspects of the development of new potential anticancer agents a multidisciplinary program is proposed. The specific aims of the proposed research are: i) Daphnopsis sellowiana, Gelsemium elegans, Catharanthus roseus, and Camptotheca acuminata, ii) determination of the structure of the biologically active compounds isolated using both spectroscopic and chemical interconversion techniques, iii) structure modification and/or synthesis of new and selected known compounds with a view to establishing unambiguous spectroscopic properties, enhancing activity and/or understanding the mechanism of action of known antitumor agents (e.g. acronycine, fagaronine, modified camptothecine derivatives, the morphinandienone system, crinasiatine and secamine derivatives), iv) conformational analysis of selected biologically active compounds, v) biosynthesis of selected antitumor antibiotics (e.g. staurosporine); vi) evaluation of selected plants for antineoplastic activity and fractionation for their active principles; and vii) investigation of the dose relationship between immune stimulation and cytotoxic activity. All isolates and synthetic intermediates will typically be evaluated against a broad range of in vitro test systems.