Natural Products and Drug Discovery and Development: A History of Success and Continuing Promise for the Future

For millennia, Nature, especially plants, has provided a source of medicines for the treatment of a wide spectrum of diseases. The isolation of plant-derived bioactive compounds, such as colchicine, morphine, and quinine in the early 1800 s, introduced a new era in medicine with the later development of pure commercial products, including morphine and the semi-synthetic drug, aspirin. The next milestone was the report by Fleming in 1929 of the serendipitous discovery of penicillin from Penicillium notatum, ushering in the 'Golden Age of Antibiotics' (1940 s-1970 s), and leading to the discovery of many other antibacterial antibiotics, including the cephalosporins, tetracyclines, aminoglycosides, glycopeptides, lipopeptides and macrocyclic compounds, as well as antifungal and antiparisitic agents. Microbes also provided models for the development of the anticholesterolemic class of drugs (statins), and a broad range of antitumor antibiotics, while plants yielded novel anticancer drugs. The intensive investigation of the marine environment began in the 1970 s, leading to the isolation of a plethora of novel, bioactive chemotypes. The first marine-derived drug, Ziconotide, based on ω-conotoxin MVIIA from the venom of Conus magus, was approved in 2005 for the treatment of chronic pain. Since then, several marine-derived anticancer agents have been approved, and a number are in clinical trials. The largely untapped potential of terrestrial flora and the marine environment, the expanding study of microbial diversity, including extremophiles and symbiotic microbes, and the fast developing field of microbial genomics, hold immense promise for the discovery and development of novel drugs and drug leads.