Royleanone Analogues from Plectranthus spp. Demonstrate P-gp Inhibition and PKC Modulation

摘要: The number of multidrug resistant (MDR) cancer cases across the globe is continuing to rise, such that the search for novel anti-cancer therapeutics is paramount. For instance, the overexpression of membrane transport proteins, such as P-glycoprotein (P-gp), or the selective modulation of protein kinases C (PKC) isoforms continues to be a major impediment to effective therapy. Known for their medicinal properties, species from Plectranthus have been reported to have cytotoxicity against various cancer cell lines due to diterpenes, such as 7α-acetoxy-6β-hydroxyroyleanone (Roy) and 6,7-dehydroroyleanone (DeRoy). Based on molecular docking simulations, 10 semi-synthetic derivatives of Roy that displayed strong P-gp interactions in silico were prepared. The antitumoral activity was evaluated in resistant human cancer cell lines NCI-H460/R and DLD1-TxR, showing three derivatives having the most prominent …