Taxol continues to show very great promise as a clinically useful agent for cancer chemotherapy. The major limitation to its further development as a chemotherapeutic agent is to assure an adequate supply of Taxol itself. Additionally this limited availability of the drug has precluded systematic evaluation of derivatives and analogs for enhanced chemotherapeutic activity. We propose a strategy to assure adequate supplies of the drug for complete clinical evaluation, drug development and ultimate clinical use. This strategy is based upon the following specific aims: Evaluation and Determination of quantitative profiles for the major taxanes in those surveyed varieties, and diurnal variation, evaluation of the influence of agronomic practices on biomass and taxane profile, study of drying and storage conditions and finally evaluation of solvents and methods for efficient and selective Taxol extraction. Once appropriate cultivars are identified development of an efficient and economic isolation process from clippings will be accomplished. This strategy presents many advantages. A proven cultural system is in place. Elements of that include a management system developed from years of experience of large scale cultivation for the nursery trade. An additional advantage is the known genetic origin and uniformity of cultivated plants. Finally, cultivation will provide high plant densities in defined locations which will significantly reduce collection and transportation costs. However, the greatest advantage of this strategy is its flexibility and responsiveness to demand. This system can be placed into production for taxol (or taxol equivalent) faster and more reliably than any other production system.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA055127-04
Application #
2096341
Study Section
Special Emphasis Panel (SRC (52))
Project Start
1991-07-18
Project End
1995-04-30
Budget Start
1994-05-01
Budget End
1995-04-30
Support Year
4
Fiscal Year
1994
Total Cost
Indirect Cost
Name
University of Mississippi
Department
Pharmacology
Type
Schools of Pharmacy
DUNS #
City
University
State
MS
Country
United States
Zip Code
38677
el Sohly, H N; Croom Jr, E M; el Kashoury, E A et al. (1997) Effect of drying conditions on the taxane content of the needles of ornamental Taxus. Planta Med 63:83-5
elSohly, H N; el-Kashoury; Croom Jr, E M et al. (1995) Effect of drying Taxus needles on their taxol content: the impact of drying intact clippings. Planta Med 61:290-1
elSohly, H N; Croom, E M; el-Kashoury, E S et al. (1994) Taxol content of stored fresh and dried Taxus clippings. J Nat Prod 57:1025-8