NCI Plant Screening Program Phase II 1986present3

In 1986, NCI initiated three 5-year contracts for a renewed plant collection program with the Missouri Botanical Garden, the New York Botanical Garden (NYBG) and the University of Illinois. The initial contracts totaled $2.7 million and the contracts were reawarded for a further 5 years to the incumbents in September 1991. Each collecting institution is currently responsible for collecting 1500 samples of 0.3-1.0 kg (dry weight) per year plus voucher samples. One of the voucher samples must be left with the national herbarium in the country of origin and another is sent to the Botany Department of the Smithsonian Institution in Washington, DC. Information on the taxonomic classification, the part of the plant collected, the date and place of collection, the habitat and any associated ethnobotanical

3 Material in this section is derived from Cragg et al. (1994a, b).

information is also delivered to NCI. Over 30000 plant samples have been shipped to the Natural Products Repository in Frederick, Maryland, between 1986 and 1992.

In this, the second phase of their plant screening program NCI will largely be evaluating plant material from tropical and subtropical countries. NYBG and its subcontractors are collecting in 13 countries in Central and South America. About one-half of NYBG's collections for NCI are contracted out to collectors in these countries. Subcontracted samples may be identified to the species level, but this depends on the expertise of the collector. NYBG remains responsible for the final product delivered to NCI.

The Missouri Botanical Garden is collecting in six African countries and the University of Illinois (and its subcontractors at the Arnold Arboretum of Harvard University and the Bishop Museum in Honolulu) are collecting in seven Asian countries. In addition to these major contractors, NCI also has a number of collaborative ventures with other institutions and researchers in which the plants of China, Korea and Polynesia and their medicinal uses are under investigation.

Of the 30000 plant samples collected to date 20000 samples have been processed into 40000 extracts. Of the 16000 tested in the anti-HIV screen, 1500 have exhibited initial bioactivity. Approximately 18 000 of the extracts have been tested against the cancer cell lines screen with 180 demonstrating a degree of activity. Some of these initial results are the activity of commonplace compounds of little interest (particularly in the case of the anti-HIV screens) and others are genuine new leads which are under further consideration.

A rainforest vine from Cameroon has demonstrated activity against both the HIV-1 and the HIV-2 forms of the AIDS virus. NCI has selected this compound, michellamine B, for pre-clinical development. A second novel compound, calanolide A, is active against HIV-1 and has also been chosen for pre-clinical work. Calanolide A is derived from a rainforest tree found initially in Sarawak, Malaysia. The range of bioactivity demonstrated by collected material in the case of calanolide A is quite variable and as a result further taxonomic and chemotaxonomic studies are necessary to discover the factors responsible for the production of this metabolite. A final compound chosen for pre-clinical development by NCI is prostratin. This potential anti-AIDS agent is found in the stemwood of the Homalanthus nutans tree which has traditional medicinal uses in Western Samoa for a number of diseases.

In summary, NCI is currently engaged in an intensive search through the tropical flora for compounds of use in the fight against cancer and

AIDS. As an ever-growing number of pharmaceutical companies are joining NCI in the quest to exploit the chemical potential of plants it is important to understand what modes of supply are available and on what terms the exchanges will be made.

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