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Keywords:

  • Natural products;
  • Terpenoids;
  • Medicinal chemistry;
  • Antitumor agents;
  • Macrocycles;
  • Euphorbiaceae

Abstract

Diterpenes occurring in plants of the Euphorbiaceae family are of considerable interest in the context of natural product drug discovery programs because of their wide range of potentially valuable biological activities and their broad structural diversity due to their different polycyclic and macrocyclic skeletons and the various aliphatic and aromatic ester groups. Euphorbia species have provided many lead compounds (resiniferatoxin, prostratin, jatrophane and pepluane esters) for drug development, some of which are currently involved in preclinical or clinical studies, but the importance of natural products of this type can be demonstrated primarily by the recent approval of ingenol 3-angelate (ingenol mebutate) by the FDA for the treatment of actinic keratosis. An appreciable time has passed since a new plant chemotype – a natural product without structural modification – has been introduced into clinical practice. Ingenol 3-angelate, a Euphorbia peplus metabolite, serves as a new prototype for natural product-based drug discovery. The aim of this paper is to provide an overview of the chemical and pharmacological potential of European Euphorbia species. Besides the main aspects of the development of ingenol 3-angelate as a drug, screening methods, isolation strategies, the chemical characteristics of Euphorbia diterpenes and the results of pharmacological investigations are surveyed.