Histone Deacetylase Inhibitory and Cytotoxic Activities of the Constituents from the Roots of Sophora Pachycarpa

Four prenylated flavonoids including isosophoranone, sophoraflavanone G, alopecurone J, alopecurone P and a resveratrol derivative HPD (2-(4-hydroxyphenyl)-2,3-dihydrobenzo[b] furan-3,4,6-triol), were isolated from the roots of Sophora pachycarpa. The cytotoxic activity of obtained compounds was evaluated against A2780, A549, HeLa, and HCT116 human cancer cell lines. We also evaluated their histone deacetylase (HDAC) inhibitory activities. Of all compounds tested, alopecurone J was the most active with IC50 values in the range of 9.97−30.91 μM against four cancer cell lines with potent pan-HDAC inhibitory activity (IC50=0.08−3.85 μM). Molecular docking experiments of these compounds with HDAC8 displayed potential selective HDAC inhibitory. Molecular docking data showed consistent results to the in vitro experiments with the high selectivity towards HDAC8. Resveratrol group plays an important role in HDAC inhibition.