Synthesis of Bioactive Diarylheptanoids from and Their Mechanism of Action for Anticancer Properties in Breast Cancer Cells.

An efficient synthesis of the -derived diarylheptanoids, viz., enantiomers of a β-hydroxyketone () and an α,β-unsaturated ketone () was developed starting from commercially available eugenol. Among these, compound showed a superior antiproliferative effect against human breast adenocarcinoma MCF-7 cells. Besides reducing clonogenic cell survival, compound dose-dependently increased the sub G1 cell population and arrested the G2-phase of the cell cycle, as revealed by flow cytometry. Mechanistically, compound acts as an intracellular pro-oxidant by generating copious amounts of reactive oxygen species. Compound also induced both loss of mitochondrial membrane potential (MMP) as well as lysosomal membrane permeabilization (LMP) in the MCF-7 cells. The impaired mitochondrial and lysosomal functions due to reactive oxygen species (ROS)-generation by compound may contribute to its apoptotic property.