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

• Published in: Phytochemistry (Oxford) 2018-01, Vol.145, p.161-167
• Main Authors: Muhit, Md. Abdul, Umehara, Kaoru, Noguchi, Hiroshi
• Format: Article
• Language: English
• Subjects: Antiestrogenic activity; Antineoplastic Agents, Phytogenic - chemistry; Antineoplastic Agents, Phytogenic - isolation & purification; Antineoplastic Agents, Phytogenic - pharmacology; Bangladesh; Cell Proliferation - drug effects; Combretaceae; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Estradiol - pharmacology; Furans - chemistry; Furans - isolation & purification; Furans - pharmacology; Glucosides - chemistry; Glucosides - isolation & purification; Glucosides - pharmacology; Haritaki; Humans; Lignan; Lignans - chemistry; Lignans - isolation & purification; Lignans - pharmacology; Molecular Structure; Plant Leaves - chemistry; Plants, Medicinal - chemistry; Structure-Activity Relationship; Terminalia citrina; Tumor Cells, Cultured; α-Keto tetrahydrofuran
• ISSN: 0031-9422; 1873-3700
• DOI: 10.1016/j.phytochem.2017.10.011

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. Terminaloside R, an anti-estrogenic α-keto furo lignan glucoside isolated from Bangladeshi medicinal plant Terminalia citrina. [Display omitted] •Seven unknown α-keto tetrahydrofuran lignan glucosides were isolated.•Absolute stereochemistry in furan ring of constituents were also characterized.•Cotton effects in their ECD spectra were practical methods for the characterization.•Terminalosides R and T inhibited estradiol-enhanced breast cancer cell proliferation.