Parthenolide and parthenolide-like sesquiterpene lactones as multiple targets drugs: current knowledge and new developments

Seca, A.M.L., Silva, A.M.S. & Pinto, D.C.G.A. (2017) Parthenolide and parthenolide-like sesquiterpene lactones as multiple targets drugs: current knowledge and new developments. Studies in Natural Products Chemistry (Bioactive Natural Products) (ed. by Atta-Ur-Rahman), 337-372. Vol 52, Chapter 9. Elsevier Science Publishers, Amsterdam, The Netherlands.

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  • Feb, 2017


Sesquiterpene lactones (SL) are secondary metabolites common in several families of plants, most prevalent in the Asteraceae but also found in fungi and invertebrates. These compounds have a 15-carbon skeleton biogenetically formed from three isoprenoid units and present a lactone moiety. They also constitute a large and diverse group of biologically active compounds that exhibit a broad spectrum of biological properties, ranging from anti-inflammatory, phytotoxic, antibacterial, and antifungal to cytotoxic/anticancer activities.

Parthenolide-like compounds belong to the germacranolide subclass of SL and are chemically characterized by a 10-membered ring with a 5-membered fused lactone, the presence of a α-methylene group and a C4-C5 epoxide ring are also characteristic in their structure. In the past few years, an increasing interest in this SL type compounds was observed, mainly due to its most noticeable member parthenolide, a natural compound that possess different biological effects and can act through several mechanisms of action, and it was also used in cancer clinical trials. Therefore, more and more research has been published on parthenolide and its analogs aiming to improved and/or discover new biological activities.

The information that will be presented herein was collected by searching the term parthenolide on Scopus, Web of Science, and PubMed databases on papers published in the last 3 years. Around 256 entries appear in our bibliographic search, from which the most relevant were selected to understand the current state of art and to give suggestions that can be used to conduct future research in the development of more effective and selective parthenolide-like drugs.

This chapter will provide a comprehensive overview of the advances on synthesis, potential therapeutic applications, structure–activity relationships, mechanism of action evidences, and pharmacology of parthenolide and parthenolide-like SL that were published in the last 3 years. Anticancer and anti-inflammatory effects will be highlighted but other important activities recently reported will also be discussed. Topics where the knowledge on parthenolide-like SL is more limited (toxicity, delivery systems, and synergistic effects) will be also mentioned. The broadest conclusion is that parthenolide and parthenolide-like SL are biologically active compounds that can become very promising drugs, especially if their use to treat human health problems, such as cancer, inflammation, bone loss, septic shock, parasite infections, just to highlight a few, turn out to be a fact. The recent results in new forms of parthenolide delivery and its synergistic effects showed that it is possible to overcome its weaknesses and its medical application seems to be plausible.