The Continuing Promise of Natural Products for Drug Development

Abstract

The past century has been a time of enormous growth in drug discovery. Synthetic organic chemistry plays a big part in this effort, but perhaps more important has been discovery of new molecules from living sources, the natural products. Notable examples are the salicylates (aspirin), the statins, and Taxol. Natural products ( syn. secondary metabolites, biologically active small molecules) play a variety of roles in the organisms that produce them, including antimicrobial, antioxidant, antifeedant, UV protectant, and a host of other actions. Newman and Cragg (2004, 2007) have illuminated the vital role that natural products play in the development of drugs with antimicrobial, antiviral, anti-inflammatory, antihyperlipidemic, anticancer, and other activities. Natural products are used directly as drugs, are modified into drugs (semisynthesis), serve as models for drugs, or provide the mechanistic details for a particular drug target. New natural-product discovery is still an important approach, with growing focus on compound sources not explored previously. These include marine sources across all domains of life, endophytic and free-living fungi and bacteria, terrestrial invertebrates, and unstudied plant groups. Many laboratories around the world, my own included, have projects focused on the discovery of drug leads from new sources and locations. From the number …