Terpenoids as therapeutic drugs and pharmaceutical agents

Abstract

Terpenoids, also referred to as terpenes, are the largest group of natural compounds. Many terpenes have biological activities and are used for the treatment of human diseases. The worldwide sales of terpene-based pharmaceuticals in 2002 were approximately US $12 billion. Among these pharmaceuticals, the anticancer drug Taxol® and the antimalarial drug Artimesinin are two of the most renowned terpene-based drugs. All terpenoids are synthesized from two five-carbon building blocks. Based on the number of the building blocks, terpenoids are commonly classified as monoterpenes (C 10), sesquiterpenes (C15), diterpenes (C20), and sesterterpenes (C25). These terpenoids display a wide range of biological activities against cancer, malaria, inflammation, and a variety of infectious diseases (viral and bacterial). In last two decades, natural-product bioprospecting from the marine environment has resulted in hundreds of terpenoids with novel structures and interesting bioactivities, with more to be discovered in the future. The problem of supply is a serious obstacle to the development of most terpenoid compounds with interesting pharmaceutical properties. Although total chemical synthesis plays a less important role in the production of some terpenoid drugs, it has contributed significantly to the development of terpenoid compounds and terpene-based drugs by providing critical information on structure-activity relationships (SAR) and chiral centers as well as generating analog libraries. Semisynthesis, on the other hand, has played a major role in the development and production of terpenoid-derived drugs. Metabolic engineering as an integrated bioengineering approach has made considerable progress to produce some terpenoids in plants and fermentable hosts. Cell culture and aquaculture will provide a solution for the supply issue of some valuable terpenes from terrestrial and marine environments, respectively. Recent advances in environmental genomics and other -omics technologies will facilitate isolation and discovery of new terpenoids from natural environments. There is no doubt that more terpenoid-based clinical drugs will become available and will play a more significant role in human disease treatment in the near future. © 2005 Humana Press Inc.