Cytotoxic 7‐Methoxylated Caged Xanthones from the Twigs of Garcinia oligantha

Main observation and conclusion Nineteen unprecedented 7‐methoxylated caged xanthones (1—19) were isolated from the twigs of Garcinia oligantha under the guidance of NMR spectroscopy. Their structures and absolute configurations were demonstrated by extensive spectroscopic data, single‐crystal X‐ray diffraction, electronic circular dichroism (ECD) calculations, and the modified Mosher's method. Compound 1 is a rare scalemic 7‐methoxylated neo‐caged xanthone, which was resolved using HPLC with CD detection on a chiral‐phase AD column, and compounds 2—3 are rare 7‐methoxylated caged xanthones with the hydrogenated Δ8(8a) double bond. Fourteen compounds exhibited promising inhibitory activities against four human cancer cell lines with IC50 values ranging from 1.9 to 14.3 μmol/L. A cell apoptosis analysis using flow cytometry showed that compound 11 could induce apoptosis in a dose dependent manner. Moreover, PARP, caspase‐9, and Bcl‐2 western blotting suggested that compound 11‐induced apoptosis may be involved in caspase‐dependent pathway. Nineteen undescribed 7‐methoxylated caged xanthones (1—19) were obtained by the NMR‐guided isolation from the twigs of Garcinia oligantha. Their absolute configurations were specified by electronic circular dichroism (ECD) calculations, X‐ray diffraction, and the modified Mosher's method. This is the first report of rare 7‐methoxylated caged xanthones (1—3) from the genus Garcinia Linn. Compounds 2, 11 and 19 exhibited potential cytotoxic activities against all of four human tumor cell lines with IC50 values ranging from 2.5 to 10.3 μmol/L. Flow cytometry analysis and western blotting showed that the compound 11‐induced HeLa cell apoptosis may be involved in caspase‐dependent pathway.