LAUSR

The aim of this study was to explore histone deacetylase inhibitory and antioxidant activities of natural products from ginger and their semi-synthetic derivatives. Two major phenolic compounds, [6]-gingerol and [6]-shogaol along with three minor phenolic compounds including [6]-gingerdione, 1-dehydro-[6]-gingerdione and [6]-gingerdiol were isolated and tested against histone deacetylase in HeLa nuclear extract. All compounds exhibited histone deacetylase inhibitory activities in micromolar concentrations. 1-dehydro-[6]-gingerdione showed the best inhibition with IC50 value of 42 μM. Thirteen semi-synthetic derivatives of two major natural products were synthesized and tested. The demethylated [6]-shogaol derivative was the best inhibitor among the synthesized compounds with IC50 value of 45 μM. Molecular docking experiments of selected compounds with representatives of class I and class II histone deacetylase isoforms revealed potential isoform-selective histone deacetylase inhibitors. The DPPH assay indicated that most derivatives possessed antioxidant activities superior to their lead compounds. Therefore, the studied compounds could serve as promising leads for safe and selective anticancer agents with histone deacetylase inhibitory and radical scavenging abilities.