Glycolipids from the aerial parts of Orostachys japonicus with fatty acid synthase inhibitory and cytotoxic activities

Inhibition of fatty acid synthase (FAS) has been proposed as a new therapeutic target for the treatment of cancer. In our preliminary study, a MeOH extract of the aerial parts of Orostachys japonicus A. Berger (Crassulaceae) inhibited FAS activity (>95% inhibition at 62.5 μg/mL). Through bioassay-guided fractionation, we isolated three cerebrosides (1–3), including one new compound (1), and seven glyceroglycolipids (4–10) from a FAS inhibitory hexane-soluble fraction of the MeOH extract of O. japonicus. On the basis of physicochemical and spectroscopic analyses including 1D and 2D NMR, HRFABMS, and ESIMS/MS, the structure of the new compound 1 was 1-O-(β-d-glucopyranosyl)-(2S,3S,4R,6Z,10E)-2-[(2′R,6′Z,9′Z)-2-hydroxyeicosa-6′,9′-dienoylamino)]-1,3,4-trihydroxytetracosa-6,10-diene, and it was named orostachyscerebroside A. Compounds 1–10 were tested for their in vitro FAS inhibitory activity, and compounds 1, 4, 5, 6, 7, and 8 inhibited the enzyme with micro-molar IC50 values both in the incorporation of [3H] acetyl CoA (from 52.2 to 108.0 μM) and in the oxidation of NADPH (from 19.5 to 30.3 μM). Interestingly, compounds 1, 4, 5, 6, 7, and 8 with FAS inhibitory activity showed cytotoxic activity against HL-60 (human leukemia) and A549 (human lung adenocarcinoma) cancer cells, while none of them displayed cytotoxicity against MCF-7 (human breast adenocarcinoma) cells. This is the first report on the inhibition of FAS by glycolipids from O. japonicus and their cytotoxic activity and may provide a scientific basis for the folk remedy using the plant to treat cancer.