The major objectives of this work is to isolate, purify and determine the structure of the anticancer compounds present in Catharanthus roseus, Catharanthus trichophyllus, Rhazya stricta, and Gnidia kraussiana. Although Catharanthus roseus is a well established source of antitumor agents of the dimeric indole alkaloid class, several highly active fractions remain to be studied for their active constituents. The crude alkaloid mixtures will be separated initially by pH gradient techniques and subsequently by column chroamtography; monitoring each step with an appropriate biological assay technique. A number of active bisindole alkaloids have been isolated and must be characterized. Isolated compounds will be identified by their mp, mass, UV and IR spectra, optical rotation CD and PMR and CMR spectra. Structure elucidation will be carried out by interpretation of these data, chemical correlation with known compounds and in particularly difficult cases by single crystal X-ray crystallography. The alkaloid fraction of the closely related plant Catharanthus trichophyllus also displays very good in vivo antitumor activity and it is proposed to isolate additional in vivo active compounds from this fraction by techniques similar to those described above for Catharanthus roseus. The Asian plant Rhazya stricta has afforded some in vitro active compounds but further isolation studies are needed on active fractions and some structural studies are still required. Rhazya orientalis will be grown for biological testing. Gnidia kraussiana has afforded a number of exceptionally cytotoxic fractions which have been obtained and it is proposed to isolate the compounds responsible for this activity. These are suspected to be tigliane or daphnane esters.
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