Drugs from Nature: Present Developments and Future Prospects

Abstract

Nature has been a source of medicinal treatments for thousands of years. While plants were the major source of medicines for millennia, the discovery of the penicillins in the 1930s ushered in the golden age of antibiotics and a revolution in chemotherapy. More recently, marine organisms have provided a host of novel bioactive chemotypes. Advances in the description of the human genome, as well as the genomes of pathogenic microbes and parasites, are resulting in the determination of the structures of many of the proteins associated with disease processes. Novel molecular targets based on these proteins are being developed as high throughput assays, which require expanded and novel chemical diversity for screening. Much of the world’s biological diversity remains unexplored as a source of novel drug leads, and the search for new bioactive agents from natural sources, including extreme environmental niches, is expanding. The potential for drug discovery is being further enhanced, with advances in procedures for microbial cultivation and the extraction of nucleic acids from environmental samples providing access to the vast untapped reservoir of microbial genetic and metabolic diversity. Genetic manipulation of microbial biosynthetic pathways is further expanding this potential to include the biosynthesis of bioactive products not generated naturally. The unique molecules generated by nature provide scaffolds for elaboration by combinatorial chemical techniques, as well as challenges to organic chemists, not only in their total synthesis, but also in the identification of simpler pharmacophores, which may prove to be equal or more effective chemotherapeutic agents. Nature thus provides access to unique molecular diversity, but the investigation of these resources requires multi-disciplinary, international collaboration in the discovery and development process.