Synthesis, anticancer activity and molecular docking study of triphenylphosphonium-linked derivatives of oleanolic acid

Lung cancer and breast cancer both are extremely threatening to humans, so it is needed to develop safe and effective drugs for the treatment of these two ailments. To improve the activity and selectivity of bioactive natural product oleanolic acid (OA), triphenylphosphonium moieties were introduced at different sites of the OA core skeleton. The in vitro antiproliferative activity screening results displayed that the anticancer activity of all target compounds was significantly improved, and some derivatives displayed strong selectivity for breast cancer cells (MCF-7) and lung cancer cells (A549) over the human normal liver cells (QSG-7701 cells). Compounds 6a (for A549 cells) and 5g (for MCF-7 cells) demonstrated the best selectivity (with SI of 12.18 and 7.72, respectively). The docking results showed that 5g and 6c could bind to and interact with PI3K protein through hydrogen bonds and intermolecular hydrophobic forces. These compounds are potential anti-MCF-7 agents and deserve further study.