α-Keto tetrahydrofuran lignan glucosides from the Bangladeshi medicinal plant Terminalia citrina inhibit estradiol (E2) induced proliferation in cancer cells

Abstract

EtOAc extract from the leaves of Terminalia citrina collected in Bangladesh were separated, and seven previously undescribed α-keto tetrahydrofuran lignan glucosides (terminalosides Q to W) were isolated and characterized. NOESY analysis of 1H NMR spectra and ECD spectroscopic data analysis revealed the absolute stereochemistry of the tetrahydrofuran ring of the isolated constituents as being a (7S,8R,8′S)- configuration in terminalosides Q to U and a (7R,8R,8′S)- configuration in terminalosides V and W. All of the isolated compounds were evaluated for their estrogenic and anti-estrogenic properties using two types of estrogen-responsive human breast cancer cell lines (MCF-7 and T47D). Terminaloside R, which has a dioxymethylene group in its aromatic ring, inhibited 90% of estradiol-enhanced cell proliferation in T47D and MCF-7 cells at concentrations of 0.01 μM and 0.1 μM, respectively. On the other hand, terminaloside T, the analogous compound which has two oxymethyl groups in place of dioxymethylene, suppressed 90% of cell proliferation selectively in T47D cells at a concentration of 0.01 μM. However, terminaloside W, the 7R-stereoisomer of terminaloside R, only showed moderate activity.