Natural products as a robust source of new drugs and drug leads: past successes and present day issues.
The history of drug development has its foundation firmly set in the study of natural remedies used to treat human disease over centuries. Analysis of medicinal plants, bioactive cultures, and increased understanding of micronutrients in the food chain opened the door to the development of purified and defined chemical compounds as dose-controlled medicines. Thus, with the early discovery of cardiotonics in foxglove, salicylic acid in willow bark, morphine in poppies, and penicillin in mold, the pharmaceutical industry was launched. Such natural small molecules served as treatments for disease and ultimately, as pharmacologic tools to enable the understanding of the biochemical pathways and mechanisms of disease. In contrast, modern drug discovery technologies coupled with the powerful tools of biotechnology have prompted drug discovery organizations to focus on target-driven drug discovery at the molecular level by launching high-throughput screening programs using artificial biochemical assays. At a time when the pharmaceutical industry has come under scrutiny for high rates of drug development failure, it is interesting to see that natural products drug discovery has been marginalized in favor of this high-throughput biochemical screening paradigm. If modern drug development is once again to benefit from natural products as a source, then the limitations of artificial biochemical assays as applied to the screening of natural extracts must be realized in order to capitalize on the vast natural molecular diversity and rich ethnobotanic data that has emerged worldwide. Natural compounds can again become central players in the treatment of disease and in the understanding of disease mechanisms.
Rishton
Gilbert M
GM
Channel Islands Alzheimer's Institute, California State University, Camarillo, CA 93012, USA. gilbert.rishton@csuci.edu
D001688:Biological Products; D015195:Drug Design; D004345:Drug Industry / Q000266:history; D019448:Ethnobotany / Q000639:trends; D049671:History, 18th Century; D049672:History, 19th Century; D049673:History, 20th Century; D006801:Humans; D010936:Plant Extracts / Q000737:chemistry* / Q000266:history; D010946:Plants, Medicinal / Q000737:chemistry*
D001688:Biological Products; D010936:Plant Extracts