The Role of Ingenane Diterpenes in Cancer Therapy: From Bioactive Secondary Compounds to Small Molecules

Diterpenes are a class of critical taxonomic markers of the Euphorbiaceae family, representing small compounds (eg, molecules) with a wide range of biological activities and multi-target therapeutic potential. Diterpenes can exert different activities, including antitumor and multi-drug resistance-reversing activities, and antiviral, immunomodulatory, and anti-inflammatory effects, mainly due to their great structural diversity. In particular, one polycyclic skeleton has been highlighted: ingenane. Besides this natural diterpene, promising polycyclic skeletons may be submitted to chemical modification-by in silico approaches, chemical reactions, or biotransformation-putatively providing more active analogs (eg, ingenol derivatives), which are currently under pre-clinical investigation. This review outlines the current mechanisms of action and potential therapeutic implications of ingenol diterpenes as small cancer molecules. (AU)