Racemic neolignans from Crataegus pinnatifida: Chiral resolution, configurational assignment, and cytotoxic activities against human hepatoma cells

Phytochemical investigation of the fruit of Crataegus pinnatifida led to the isolation of four pairs of dihydrobenzofuran neolignan enantiomers (1a/1b-4a/4b) including six new compounds (1a/1b, 2a/2b, 3a and 4a). The enantioseparations of the racemates were achieved successfully by chiral chromatographic column. Their structures were established by comprehensive spectroscopic analyses and the absolute configurations were determined by quantum mechanical calculation of electronic circular dichroism (ECD) spectra. All compounds were evaluated in vitro for their cytotoxicity using human hepatocellular carcinoma Hep3B and HepG2 cells. Among them, it was found that 2a had a selective cytotoxicity against Hep3B cells with IC50 value of 25.47 mu M, while the IC50 value of its enantiomer 2b on Hep3B cells was 59.37 mu M. These results implied that the absolute configurations of 2a and 2b possessed remarkable influences on their cytotoxicity. Further flow cytometry analysis indicated that 2a performed more significant effect on cell apoptosis compared with its enantiomer 2b.