New histone deacetylase inhibitors and anticancer agents from Curcuma longa

The aims of this study were to explore histone deacetylase inhibitory and antioxidant activities of curcuminoids as well as derivatives of curcumin. Curcumin ( 6 ), demethoxycurcumin ( 7 ), dihydrocurcumin ( 8 ), bisdemethoxycurcumin ( 9 ), and hydroxycurcumin ( 10 ) were isolated and tested against histone deacetylases in HeLa nuclear extract. Hydroxycurcumin ( 10 ) showed the best inhibition among the isolated compounds. Some curcumin derivatives were also prepared and tested. The potential derivatives were tested on five cancer cell lines. All compounds exhibited slightly weaker antiproliferative activities against cancer cells and less toxic to non-cancer cells than curcumin ( 6 ). The least toxic derivative ( 17 ) exhibited the best antiproliferative activity against human cervical cancer cell lines (HeLa) with the IC 50 value of 4.69 ± 0.14 μM. The most active histone deacetylase inhibitor ( 19 ) showed the highest potency against human colon cancer cell lines (HCT116) and the selective binding to HDAC4 based on molecular docking experiments. Most derivatives possessed antioxidant activities superior to curcumin. The results suggested potential candidates for anticancer agents.