Triterpenoids from the resin of Styrax tonkinensis and their antiproliferative and differentiation effects in human leukemia HL-60 cells

Four new triterpenoids, 6 beta-hydroxy-3-oxo-11R, 12R-epoxyolean-28,13 beta-olide ( 1), 3 beta, 6 beta-dihydroxy-11 alpha, 12 alpha-epoxyolean-28, 13 beta-olide ( 2), 3 beta, 6 beta-dihydroxy-11-oxo-olean-12-en-28-oic acid ( 3), and 3 beta-hydroxy-12-oxo-13H alpha-olean-28, 19 beta-olide ( 4), and five known triterpenes, 19 alpha-hydroxy-3-oxo-olean-12-en-28-oic acid ( 5), 6 beta-hydroxy-3-oxo-olean-12-en-28-oic acid ( 6), sumaresinolic acid ( 7), siaresinolic acid ( 8), and oleanolic acid ( 9), were isolated from the resin of Styrax tonkinensis. The structures of these triterpenoids were determined by physicochemical and spectroscopic methods. The configuration of compound 4 was confirmed by X-ray crystallographic analysis. All these triterpenoids inhibited HL-60 cell growth with IG(50) values ranging from 8.9 to 99.4 mu M. Oleanolic acid ( 9) was the most effective antiproliferative agent, with an IG(50) value of 8.9 mu M. While 3 beta, 6 beta-dihydroxy-11-oxo-olean-12-en-28-oic acid ( 3) exhibited the least effective growth inhibition among these triterpenoids, it induced HL-60 cells to undergo differentiation as measured by an NBT reduction assay.