Abietane Diterpenoids from Plectranthus spp. as a starting tool in Cancer Research

Natural products from medicinal plants represent an important source of novel therapeutic substances to fight severe diseases including cancer. The Plectranthus genus is commonly used in traditional medicine due to its potential to treat several illnesses. Diterpenoids are commonly found in Plectranthus spp., and have a widespread spectrum of biological activity, namely anticancer properties.

Protein kinase C (PKC) family isoforms have been the focus of intense research, and are recognized as therapeutic targets in anticancer drug development. In this work, a small library of abietane derivatives was studied for their ability to activate PKC isoforms. To obtain the lead molecules, several extraction methods were tested to optimize the extraction of the bioactive diterpenoid 7α-acetoxy-6β-hydroxyroyleanone (Roy). The results obtained revealed potent activators of PKC family proteins, namely: a selective activator of PKCδ, the 7α-acetoxy-6β-benzoyloxy-12-O-benzoylroyleanone (RoyBz). The patented diterpenoid RoyBz was prepared using Roy as starting material. RoyBz potently inhibited the proliferation of colon cancer cells by inducing a PKCδ-dependent mitochondrial apoptotic pathway involving caspase-3 activation. The results indicate that RoyBz targets drug resistant cancer stem cells, in HCT116 colon cancer cells, preventing tumor dissemination and recurrence. These results point to promising activators of PKCs with high potency and isoform-selectivity that may emerge from the exploitation of this new family of abietane diterpenoids. Molecular docking studies are currently ongoing to further identify new selective abietane diterpenoids as new PKC modulators.

Publication History

Article published online:
13 December 2021