Sesquiterpene lactones (STLs) are a group of naturally occurring compounds, most of them found in the Asteraceae family but also present in Apiaceae, Magnoliaceae, and Lauraceae. To date about 8000 compounds have been reported. They consist of a C15 backbone with numerous modifications resulting in a variety of structures but with the common feature of a γ-lactone ring. They are classified in four major groups: germacranolides, eudesmanolides, guaianolides, and pseudoguaianolides, though there are other subtypes. There has been an increasing interest in sesquiterpene lactones due to the wide range of biological activities they present. Among the activities found, antimicrobial, antitumor, anti-inflammatory, antioxidant, antiulcerogenic, molluscicidal, antihelminthic, hepatoprotective and hepatotherapeutic, antiprotozoal, antidepressant, and bitter properties have been described. Besides, they play an important role in the interaction of plants with insects acting as attractants, deterrents, and antifeedants. These compounds were considered at first highly cytotoxic, but chemical transformations have enhanced their biological activities and diminished their cytotoxicity, so considerable attention has been drawn again on them as lead molecules. Artemisinin derivatives, artesunate, and artemether are drugs currently being employed, and dimethylaminoparthenolide, a parthenolide synthetic analogue, and mipsagargin, a prodrug from thapsigargin, are under clinical trials.
A summary with the most important findings about the known sesquiterpene lactones, artemisinin, parthenolide, cynaropicrin, dehydroleucodine, mexicanin, helenalin, costunolide, santonin, arglabin, and thapsigargin, will be given.
Studies about the adverse health effects, toxicity, and ecological roles of some sesquiterpene lactones are also mentioned.
KeywordsSesquiterpene lactones Chemical aspects Biological activities Adverse effects Toxicity
- Abderrazak A, El Hadri K, Bosc E et al (2016) Inhibition of the inflammasome NLRP3 by arglabin attenuates inflammation, protects pancreatic β-cells from apoptosis, and prevents type 2 diabetes mellitus development in ApoE2Ki mice on a chronic high-fat diet. J Pharmacol Exp Ther 357(3):487–494. https://doi.org/10.1124/jpet.116.232934 CrossRefPubMedGoogle Scholar
- Chaturvedi D (2011) Sesquiterpene lactones: structural diversity and their biological activities. In: Tiwari VK, Mishra BB (eds) Opportunity, challenge and scope of natural products in medicinal chemistry. Research Signpost, Kerala, pp 313–334. ISBN: 978-81-308-0448-4Google Scholar
- Da Silva CF, Da Gama JB, De Araujo JS et al (2013) Activities of psilostachyin a and cynaropicrin against Trypanosoma cruzi in vitro and in vivo. Antimicrob Agents Chemother 57(11):5307–5305Google Scholar
- Fischer NH, Oliver EJ, Fischer HD (1979) The biogenesis and chemistry of sesquiterpene lactones. In: Herz W, Grisebach H, Kirby GW (eds) Progress in chemistry of organic natural products, vol 38. Springer, New York, pp 47–390Google Scholar
- Heywood VH, Harbone JB, Turner BL (1977) An overture to the Compositae. In: Heywood JB, Harbone JB, Turner BL (eds) The biology and chemistry of the Compositae, vol 1. Academic Press, New York/London, pp 1–20Google Scholar
- Hohmann M, Longhi-Balbinot D, Guazelli C et al (2016) Sesquiterpene lactones: structural diversity and perspectives as anti-inflammatory molecules. In: Atta-ur-Rahman FRS (ed) Studies in natural products chemistry: bioactive natural products, vol 49. Elsevier, Amsterdam, pp 313–334Google Scholar
- Inspyr Therapeutics Inc. (Texas, USA) (2016) Inspyr Therapeutics announces mipsagargin Ph 2 trial for patients with clear cell renal cell carcinoma expressing PSMA. http://www.inspyrtx.com/news/press-releases/detail/625/inspyr-therapeutics-announces-mipsagargin-ph-2-trial-for. Accessed 18 Aug 2016
- Knudsmark Jessing K, Duke S (2014) Potential ecological roles of artemisinin produced by Artemisia annua L. J Chem Ecol. https://doi.org/10.1007/s10886-014-0384-6
- Lezama Dávila CM, Satoskar AR, Úc Encalada M et al (2007) Leishmanicidal activity of artemisinin, deoxoartemisinin, artemether and arteether. Nat Prod Comm 2(1):1–4Google Scholar
- Lin X, Peng Z, Su C (2016) Potential anti-cancer activities and mechanisms of costunolide and dehydrocostuslactone. Int J Mol Sci 16(5):10888–10906Google Scholar
- Liu YH (2013) Progress in the research of structure and pharmacological activity of parthenolide (review). Chin J Pharm Biotechnol 20(6):586–589Google Scholar
- The Society for Medicinal Plant and Natural Product Research (2017) Nobel Prize for the discovery of natural product-derived drugs. https://www.ga-online.org/events-2/ifpvgksc21/Nobel-Prize-for-the-discovery-of-natural-productderived-drugs-. Accessed 8 Aug 2016
- Yoshioka H, Mabry TJ, Timmerman B (1973) Sesquiterpene lactones. University of Tokio Press, TokioGoogle Scholar