title: Natural products: a continuing source of novel drug leads.
abstract: BACKGROUND
  Nature has been a source of medicinal products for millennia, with many useful drugs developed from plant sources. Following discovery of the penicillins, drug discovery from microbial sources occurred and diving techniques in the 1970s opened the seas. Combinatorial chemistry (late 1980s), shifted the focus of drug discovery efforts from Nature to the laboratory bench.
  
  
  METHODS
  This review traces natural products drug discovery, outlining important drugs from natural sources that revolutionized treatment of serious diseases. It is clear Nature will continue to be a major source of new structural leads, and effective drug development depends on multidisciplinary collaborations.
  
  
  CONCLUSIONS
  The explosion of genetic information led not only to novel screens, but the genetic techniques permitted the implementation of combinatorial biosynthetic technology and genome mining. The knowledge gained has allowed unknown molecules to be identified. These novel bioactive structures can be optimized by using combinatorial chemistry generating new drug candidates for many diseases.
  
  
  CONCLUSIONS
  The advent of genetic techniques that permitted the isolation / expression of biosynthetic cassettes from microbes may well be the new frontier for natural products lead discovery. It is now apparent that biodiversity may be much greater in those organisms. The numbers of potential species involved in the microbial world are many orders of magnitude greater than those of plants and multi-celled animals. Coupling these numbers to the number of currently unexpressed biosynthetic clusters now identified (>10 per species) the potential of microbial diversity remains essentially untapped.
authors: Division of Cancer Treatment and Diagnosis, Frederick National Laboratory for Cancer Research, Frederick, MD 21702-1201, USA.
authors: Gordon M
authors: GM
authors: Cragg
authors: David J
authors: DJ
authors: Newman
mesh_terms: D000818:Animals; D001419:Bacteria / Q000737:chemistry / Q000235:genetics; D003001:Cloning, Molecular; D055808:Drug Discovery / Q000266:history / Q000379:methods*; D049673:History, 20th Century; D049674:History, 21st Century; D006801:Humans; D010944:Plants / Q000737:chemistry / Q000235:genetics