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Plant Derived Bioactive Chemicals 



quantities for this work, recollection and taxonomic screening for higher yielding 

 strains, or producers of chemical analogues may occur. It is usual for many 

 plant extracts to be followed simultaneously with 'hits from other natural product 

 sources such as microbes and marine organisms, as well as synthetic chemical 

 libraries. All along the way, positive results in more advance biological models, 

 identification in the literature for known chemicals produced by the plant and 

 information about possible related ethnobotanical uses of a plant, keeps the 

 necessary level of enthusiasm for following the 'hit'. In this way, an exciting and 

 fast pace race is run until an extensive structure/ activity relationship is 

 developed and a 'hit' becomes a 'lead compound'. At the same time, a plant 

 extract will be tested in many other screens running in parallel, and a plant 

 extract which fails in one screen may yield actives in another. Thus a plant can 

 never be described as having no value. All this amounts to a multimillion dollar 

 annual investment in which the plants are playing their predicted role in 

 producing many useful hits and a number of promising novel structure/activity 

 relationships. 



Although it is too early to see how the plants will fair in this race for new 

 medicines (it takes 10-15 years to get a new medicine to the market and only an 

 estimated five out of 10,000 leads makes it to the market place), it should be noted 

 that Searle is presently pursuing Butyl-DNJ, a potentieJ AIDS medicine, through 

 early phase clinical trials. The natural chemical, DNJ, was isolated from plant 

 materials and shown active in in-vitro cell culture assays by a group working in 

 Kew Gardens in the UK on insect antifeedants fi-om mulberry trees. The native 

 compound was too toxic to be useful, but after a number of analogues were then 

 made £md tested, and Butyl DNJ was made and shown to have the necessary 

 properties to be advanced into the clinic. 



Monsanto also has an agricultural discovery program which benefits from this 

 project. Some of the samples shipped to Monsanto are extracted for proteins 

 which are screened for the desired biological activity against plant diseases. 

 Active proteins are purified, sequenced and the gene responsible for its production 

 identified. This gene can then be cloned into plants to enhance the performance 

 and productivity of crops which yield both food and materials. Extracts enriched 

 in small chemicals are also screened for activity against crop diseases or weeds. 

 Active chemicals from these extracts are isolated and their structures elucidated 

 as described for human medicines. 



This program has facilitated Missouri Botanical Garden's botanical collecting 

 and specimen acquisition for North American plants. Each herbarium specimen 

 is a modem record of species distribution, tying in with the efiForts of the 'Flora of 

 North America' project, coordinated by the Missouri Botanical Garden, to 

 document the distribution of all species that exist in the United States, Canada 

 and Greenland. This ultimately will provide some of the botanical data essential 

 to the establishment of a National Biodiversity Survey. 



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