Enantiomeric chromene derivatives with anticancer effects from Mallotus apelta

Mallotus apelta (Lour.) Mull.Arg has been used in traditional medicine for the treatment of chronic hepatitis. Six new chromene derivatives, malloapeltas C-H (1-6) and one known compound, malloapelta B (7) were isolated and structured from the leaves of M. apelta. Two pairs of enantiomers (1a/1b and 2a/2b) were successfully separated by chiral high-pressure liquid chromatography (HPLC). The structures and absolute configurations of compounds were determined using spectroscopic methods, including 1D, 2D NMR, and MS and quantum chemical calculation methods. All compounds were evaluated for cytotoxic activity using cell counting kit-8 (CCK-8) assay against ovarian cancer cell line (TOV-21G). Compounds 1-5 and 7 exhibited significant growth and viability inhibitory effects with GI(50) values ranging from 0.06 to 10.39 mu M and IC50 values ranging from 1.62 to 10.42 mu M on ovarian cancer cell line, TOV-21G. The most cytotoxic compounds 2, 3, and 7 were chosen for studying in apoptosis mechanism. Compounds 2, 3, and 7-induced apoptosis as evidenced by activated caspase 8, caspase 9, and PARP, increased Bak and Bax, and decreased Bcl-xL and survivin. Moreover, compounds 2, 3, and 7 significantly inhibited the NF-kappa B signaling pathway. Taken together, our findings propose the potential application of compounds 2, 3, and 7 for treating cancer via modulating NF-kappa B activity.