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Plant Derived Bioactive Chemicals 



Table 1. Roles of natural products and screening in the development of the top 

 selling U.S. medicines. 



The top twenty best selling U.S.A. drugs with total sales approaching 6 billion 

 dollars in 1988 (data supplied by IMS hitemational) fall into 11 therapeutic 

 classes. The role of natural products research in the development and 

 understanding of these therapeutic classes and the role of screening in 

 discovering the lead compound which resulted in these drugs, was abstracted 

 mainly from the work of Sneader (1986); other general references were Oilman et 

 al. (1990) and that for Mevacor from Vagelos (1991). 



Natural products from exogenous sources (plants, microbes, and non- 

 mammalian animal tissues) were involved in understanding the pharmacology 

 of all therapeutic classes with the exception of female sex hormones, which were 

 isolated from mammalian tissue. In eight of these therapeutic classes, the 

 natural chemicals were used therapeutically as is, or as synthetic chemical 

 derivatives, to treat human ailments at one stage in the development of the 

 current medicines. Three of the classes still use naturally derived chemicals in 

 their current products. 



The role of screening in the development of these medicines was discerned by 

 identifying how the lead compound (the direct bioactive chemical ancestor of a 

 drug) was discovered. This analysis indicates that the twenty top selling drugs 

 were developed from fourteen lead compounds. Random screening, where no 

 significant structure preconditions were used to select the compound, resulted in 

 seven of the fourteen leads. Analogue synthesis and testing, where structures of 

 a hormone or an enzyme's substrate were used to synthesize analogues, resulted 

 in the discovery of three of the fourteen lead compounds. Unexpected 

 observations, whether in the clinic or during screening, were responsible for the 

 discovery of three of the fourteen lead compounds. In the case of the female sex 

 hormones, the lead compound was the natural biochemical itself This is in 

 contrast with the other leads which antagonize the activity of biological molecules. 



Table 1 cont 



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