(±)-Quassidines I and J, Two Pairs of Cytotoxic Bis-β-carboline Alkaloid Enantiomers from Picrasma quassioides

(+/-)-Quassidines I (1) and J (2), two pairs of new bis-beta-carboline alkaloid enantiomers, were isolated from the stems of Picrasma quassioides. Their structures were determined by the analysis of spectroscopic data, including HRESIMS and 2D NMR, and confirmed by single-crystal X-ray diffraction analysis. The racemic mixtures of 1 and 2 were resolved into two pairs of enantiomers, (+)-S-1a and (-)-R-1b and (+)-S-2a and (-)-R-2b, by HPLC using a chiral Daicel IB-3 column, respectively, which represents the first successful example to resolve bis-beta-carboline racemic mixtures. The absolute configurations of the two pairs of enantiomers were determined by comparison between the calculated and experimental ECD spectra. The cytotoxicity evaluation revealed that (+)-S-1a and (+)-S-2a showed more potent cytotoxicity against human cervical HeLa and gastric MKN-28 cancer cell lines with IC50 values of 4.03-6.30 mu M than their enantiomers with IC50 values of 9.64-12.3 mu M; however, the two (+)-S-quassidines showed similar activities to their enantiomers against the mouse melanoma B-16 cancer cell line.