(−) and (+)-Merrilliaquinone, a pair of new quinone enantiomers from Illicium merrillianum and their distinctive effect on human hepatoma and hepatic cells

Abstract

Merrilliaquinone (1), a new racemic quinone was isolated from the branches and leaves of Illicium merrillianum. Chiral separation of 1 gave two enantiomers (−)-merrilliaquinone (1a) and (+)-merrilliaquinone (1b). The structure of 1 was established by comprehensive spectroscopic analysis, and the absolute configurations of 1a and 1b were determined by quantum mechanical calculation of ECD spectra. It is very interesting that 1b had a selective cytotoxicity against human hepatoma cell lines SMMC7721 and HuH7 with IC₅₀ values of 0.91 μM and 1.29 μM, while its IC₅₀ values on normal human hepatic cells QSG7701 and LO2 were 47.79 μM and 36.71 μM, respectively. Moreover, 1a and racemate 1 only exhibited very weak cytotoxicity against SMMC7721 and HuH7 cells with IC₅₀ values of 27.01–37.82 μM. These results implied that the absolute configurations of 1a and 1b possess remarkable influences on their cytotoxicities. Further mechanism studies indicated that 1b dose-dependently induced SMMC7721 cell apoptosis and reduction of mitochondrial membrane potential (MMP) at 1–10 μM. Flow cytometry analysis showed that the 1b-induced SMMC7721 cell apoptosis was associated with cell cycle arrest during the G₀/G₁ phase.