Synthesis, Anticancer Activity, Structure‐Activity Relationship and Mechanistic Investigations of Falcarindiol Analogues

Abstract

Forty samples of optically active falcarindiol analogues are synthesized by using the easily available C2 symmetric (R)- and (S)-1,1'-binaphth-2-ol (BINOL) in combination with Ti(Oi Pr)4 , Zn powder and EtI. Their anticancer activities on Hccc-9810, HepG2, MDA-MB-231, Hela, MG-63 and H460 cells are assayed to elucidate their structure-activity relationships. These results showed that the falcarindiol analogue (3R,8S)-2 i with the terminal double bond has the most potent anti-proliferation effect on Hccc-9810 cells with IC50 value of 0.46 μM. The falcarindiol analogue (3R,8S)-2 i can induce obvious Hccc-9810 cell apoptosis in a concentration-dependent manner by Hoechst staining and flow cytometry analysis. The proposed mechanism suggests that the falcarindiol analogue (3R,8S)-2 i increases LDH release and MDA content, and reduces the levels of SOD activity, which lead to the accumulation of oxidative stress and induce apoptosis in Hccc-9810 cells.