Polyoxypregnane Ester Derivatives and Lignans from Euphorbia gossypina var. coccinea Pax.

From the aerial parts of Euphorbiagossypina var. coccinea Pax., eight new pregnane glycosides (euphogossypins A-H, 1-8) of the cynanforidine and deacetylmetaplexigenin aglycons, two new lignans (gossypilignans A and B, 9 and 10), and four known compounds, namely, the pregnane 12-O-benzoyldeaxcylmetaplexigenin (11), the lignan 9α-hydroxypinoresinol (12), and the flavonoids naringenin (13) and quercitrin (14) were isolated. The structure elucidation of the new compounds was carried out by a spectroscopic analysis, including HRMS, 1D (1H, 13C JMOD), and 2D NMR (HSQC, 1H-1H COSY, HMBC, and NOESY) experiments. The obtained pregnane glycosides were substituted with acetyl and benzoyl ester moieties, and sugar chains containing thevetose, cymarose, digitoxose, and glucose monosaccharides. All of the compounds are described for the first time from E. gossypina var. coccinea. The isolated pregnanes and lignans were tested for their antiproliferative activity on HeLa cells using the MTT assay; the compounds exerted no significant effect against the tumor cells.

Jacaranone Derivatives with Antiproliferative Activity from Crepis pulchra and Relevance of This Group of Plant Metabolites.

Jacaranones are a small group of specific plant metabolites with promising biological activities. The occurrence of jacaranones is limited to only a few plant families, with Asteraceae being the most abundant source of these compounds. Therefore, jacaranones can also serve as chemotaxonomic markers. Our phytochemical investigation of Crepis pulchra L. (Asteraceae) resulted in three jacaranone derivatives (jacaranone, 2,3-dihydro-2-hydroxyjacaranone, 2,3-dihydro-2-methoxyjacaranone), and (6R,9S)-3-oxo-α-ionol-ß-d-glucopyranoside, fulgidic acid, 12,15-octadecadienoic acid methyl ester, scopoletin and apigenin-7-O-ß-d-glucoside. This is the first report on the isolation of jacaranones from a species belonging to the Cichorioideae subfamily of Asteraceae. Jacaranone derivatives were subjected to an in vitro antiproliferative assay against a panel of human cancer cell lines (MCF-7, MDA-MB-231, HeLa, and C33A), revealing high or moderate activities, with IC50 values ranging from 6.3 to 26.5 µM.

Ingol and Ingenol-Type Diterpenes from Euphorbia trigona Miller with Keratinocyte Inhibitory Activity.

Ingenol mebutate, isolated from Euphorbia peplus, is an ingenane-type diterpenoid, primarily used for the topical treatment of actinic keratosis, a premalignant skin condition. The aim of our work was to investigate other Euphorbia species to find structurally similar diterpenes that can be used as alternatives to ingenol mebutate. Pharmacological investigation of Euphorbia candelabrum, Euphorbia cotinifolia, Euphorbia ramipressa, and Euphorbia trigona revealed the potent keratinocyte (HPV-Ker cell line) inhibitory activity of these spurge species. From the methanolic extract of the aerial parts of Euphorbia trigona Miller, the most active species, five ingol (1-5) and four ingenane-type diterpenoids (6-9) were isolated by various chromatographic separation techniques, including open column chromatography, vacuum liquid chromatography, thin-layer chromatography, and high-performance liquid chromatography. The structures of the compounds were determined by NMR spectroscopic analysis and by comparison of the assignations with the literature data. The cytotoxic activity of the compounds against keratinocytes was tested in vitro by using ingenol mebutate as a positive control. Among the isolated compounds, two ingenane derivatives (6 and 7) exhibited remarkably stronger cytotoxic activity (IC50 values 0.39 µM and 0.32 µM, respectively) on keratinocytes than ingenol mebutate (IC50 value 0.84 µM). These compounds could serve as starting materials for further investigations to find alternatives to Picato® (with active substance ingenol mebutate), which was withdrawn from marketing authorization in the European Union.

Chemistry and Pharmacology of Cyperaceae Stilbenoids: A Review.

Cyperaceae is a cosmopolitan plant family with approx. 5000 species distributed worldwide. Several members of this family are used in traditional medicines for the treatment of different diseases. In the last few decades, constituents with great chemical diversity were isolated from sedges, and a wide range of biological activities were detected either for crude extracts or for pure compounds. Among the isolated compounds, phenolic derivatives are the most important, especially stilbenoids, and flavonoids. To date, more than 60 stilbenoids were isolated from 28 Cyperaceae species. Pharmacological investigation of Cyperaceae stilbenoids revealed that several compounds possess promising activities; mainly antiproliferative, antibacterial, antioxidant and anthelmintic effects. Isolation, synthesis and pharmacological investigation of stilbenes are increasing constantly. As Cyperaceae species are very good sources of a wide variety of stilbenes, and several of them occur in large amount worldwide, they are worthy for phytochemical and pharmacological investigations. Moreover, stilbenes are important from chemotaxonomical point of view, and they play a key role in plant defense mechanisms as well. This review summarizes the stilbenoids isolated from sedges, and their biological activities.