Cytotoxic constituents of Picramnia latifolia and Vitex negundo.

摘要

Cell-based bioassay-guided fractionation was carried out on the chloroform-soluble extracts of both the roots and leaves of Picramnia latifolia, which were collected in Peru. A new chrysophanol benzanthrone, two new chrysophanol anthrone C-glycosides, two new chrysophanol oxanthrone C-glycosides, and six known anthraquinones, chrysophanol, 1,5-dihydroxy-3-methyl-anthraquinone, 4-methyl-6,8-dihydroxy-7H-benz[de]-anthracen-7-one, pulmatin, chrysophanein, and nataloe-emodin, together with 7-hydroxycoumarin, 6-methoxy-7-hydroxycoumarin, β-sitosterol, and β-sitosterol glucoside, were isolated. The structures of the new secondary metabolites isolated in this investigation were established by spectroscopic methods, including 1D- and 2D-NMR, high-resolution mass spectrometric analysis, and circular dichroism (CD) experiments. The cytotoxic activity of the compounds isolated from Picramnia latifolia was evaluated in a small panel of human cancer cell lines. Picramnioside H, mayoside D, and mayoside E showed weak cytotoxic activity, while the known anthraquinone nataloe-emodin showed more potent cytotoxic activity (ED₅₀ 5 μg/mL) against the cell lines tested. Nataloe-emodin was chosen for in vivo evaluation in a hollow fiber assay, but at the doses tested it was found to be inactive.; A chloroform-soluble extract of the leaves of Vitex negundo L. (Verbenaceae), exhibited significant cytotoxic activity against a panel of six human cancer cell lines, with ED₅₀ values ranging between 0.4 to 7.5 μg/mL. Bioassay-guided fractionation, monitored with Lu1 (human lung cancer) cells of this chloroform-soluble extract, led to the isolation of the known flavone, vitexicarpin, as the active component, together with the inactive known compounds, β-sitosterol, β-sitosterol glucoside, 4-hydroxybenzoic acid, and luteolin. Vitexicarpin exhibited strong cytotoxicity for most of the cell lines tested, except for Col2 (colon cancer), with an ED₅₀ range of 0.2–0.8 μg/mL. A series of acylation reactions was performed on vitexicarpin, leading to the generation of quercetogetin, 5,3′-diacetoxy-3,6,7,4′-tetramethoxyflavone, and six new acylated analogues. Of these, 5,3′-dihexanoyloxy-3,6,7,4 ′-tetramethoxyflavone was selected for follow-up in vivo testing in the hollow fiber and the in vivo P-388 lymphocytic leukemia models. However, this compound was found to be inactive in both these in vivo assays. Therefore, 5,3 ′-dihexanoyloxy-3,6,7,4′-tetramethoxyflavone was not considered further as a potential cancer chemotherapeutic agent.