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

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((OPr)-Pr-i)(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 mu M. 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.

Automated summary

In this study, 40 optically active falcarindiol analogues were synthesized and their anticancer activities on various cell lines were evaluated. The results indicated that the falcarindiol analogue (3R,8S)-2 i with a terminal double bond exhibited the most potent anti-proliferation effect on Hccc-9810 cells, inducing apoptosis through increased LDH release and MDA content, and decreased SOD activity, leading to oxidative stress accumulation.