Bioactive drimane sesquiterpenoids and aromatic glycosides from Cinnamosma fragrans

Abstract

Phytochemical investigation of the ethyl acetate and methanol extracts of the bark of Madagascan endemic and medicinal plant Cinnamosma fragrans led to the isolation of two drimane sesquiterpene derivatives: cinnafragroside A (1) and cinnafragrin E (2), two aromatic glycosides: 3,4,5-trimethoxyphenol 1-O-β-d-apiofuranosyl-(1→6)-β-d-glucopyranoside (3) and 3,4-dimethoxyphenyl-1-O-β-d-apiofuranosyl-(1→6)-β-d-glucopyranoside (4), together with 12 known compounds identified as: helicide (6), 1-(α-l-rhamnosyl(1→6)-β-d-glucopyranosyloxy)-3,4,5-trimethoxybenzene (7), vanilloloside (8), cinnamadin (9), ugandensolide (10), cinnamosmolide (11), cinnamolide (12), polygodial (13), cinnamodial (14), bemadienolide (15), 4-isopropyl-6-methyl-α-tetralone (16), and capsicodendrin (17). Another new compound, 11-norcinnafragrolide-9-one (5), was obtained during chemical derivatization of capsicodendrin and gave a hint to understanding the structure required for the antiproliferative activity of 17. The structures of the new compounds were elucidated based on the interpretation of their spectroscopic data including one and two dimensional nuclear magnetic resonance (1D- and 2D-NMR) and mass spectroscopic data. All isolated compounds were evaluated against the hormone dependent breast cancer cell line MCF-7. Compound 17 exhibited the most potent activity with an IC50 value of 0.6μM. Our preliminary SAR study showed that the hydroxyl group at C-12′ and the presence of conjugated carbonyl contribute to the antiproliferative activity.