36 



Plant Derived Bioactive Chemicals 



Introduction 



Monsanto is a world wide development, manufacturing and marketing company 

 of high value agricultural and chemical products, pharmaceuticals (Searle) and 

 food ingredients (NutraSweet) with 1992 sales of $7.8 billion. Over the past four 

 years Monsanto has collaborated with the Missouri Botanical Gardens to obtain 

 approximately 10,000 plant samples from the United States and Puerto Rico. The 

 rationale for and utility of this activity to Monsanto's ongoing drug and 

 agrochemical discovery programs is described. 



Nature has been, is, and will continue to be, a key source for the discovery of new 

 products of value to humanity. The plants of the earth's ecosystems have proven 

 to be mankind's medicine chests. Eighty percent of people in developing countries 

 rely on medicines derived from plants (Famsworth, 1990). These people generally 

 have an intimate knowledge of their medicinal flora and exploit a wide variety of 

 species. Drugs derived from plants are a major part of the pharmacopeia of 

 western medicine as well, many adopted from traditional folk remedies. The 

 early European botanical gardens were primarily collections of medicinal plants 

 rather than display gardens. The plants then formed the basis of western 

 medicine. 



The importance of natural chemicals in the development of Western medicine can 

 be illustrated by studying the evolution of the twenty best-selling drugs in the 

 United States. This analysis demonstrates that most of these modern medicines 

 (which accounted for six billion dollars in sales in 1988) have benefitted from 

 natural products research. Plants had a key role to play in the development of 

 seven of these twenty medicines, supplying either the medicines themselves, 

 leads for medicinal chemists, or precursors for drug S3Tithesis (Table 1). Of all of 

 the medicines marketed in the United States, Farnsworth (1990) has estimated 

 that 199 or about 25% contain active ingredients extracted from plants. The value 

 of the medicines derived directly or indirectly from natural resources in 1984 was 

 estimated at greater than 20 billion dollars (Farnsworth, 1984). The figures above 

 indicate that directly or indirectly, the majority of western medicines owe their 

 existence to natural products research. 



DLscoverv of Modem Medicines 



Advances in medicinal science during the last century led to the realization that 

 specific chemical compounds are responsible for the effects of drugs. During this 

 century research into the mode of action of these bioactive chemicals has shown 

 that they have utility because they inhibit or stimulate specific target molecules 

 (usually protein-based receptors or enzymes) in the diseased animal. In addition, 

 the direct ancestors (leads) of today's top drugs were found by random screening 

 or analogue synthesis and testing, or else by chance observation (Table 1). 



Pagie2 



