Intriguing steroid glycosides for cancer therapy by suppressing the DNA damage response and mTOR/S6K signaling pathways.

Two rare 8-hydroxysteroid glycosides (6-7), and their downstream metabolites (1-5) with an unprecedented 6/6/5/5/5-pentacyclic scaffold, together with seven known analogues (8-14) were isolated from the twigs and leaves of Strophanthus divaricatus. Their structures were fully assigned by analysis of the spectroscopic and ECD data, NMR calculations, X-ray crystallographic study, and chemical methods. In addition, the inhibitory effects of 1-14 on liver and lung cancer cell lines were evaluated, and preliminary structure-activity relationship was discussed. Data-independent acquisition (DIA)-based quantitative proteomic analysis and biological verification of H1299 cells suggested that this family of compounds may play an anticancer role by suppressing both DNA damage response (DDR) and mTOR/S6K signaling pathways.

Triterpene and Steroid Glycosides from Marine Sponges (Porifera, Demospongiae): Structures, Taxonomical Distribution, Biological Activities.

The article is a comprehensive review concerning tetracyclic triterpene and steroid glycosides from sponges (Porifera, Demospongiae). The extensive oxidative transformations of the aglycone and the use of various monosaccharide residues, with up to six possible, are responsible for the significant structural diversity observed in sponge saponins. The saponins are specific for different genera and species but their taxonomic distribution seems to be mosaic in different orders of Demospongiae. Many of the glycosides are membranolytics and possess cytotoxic activity that may be a cause of their anti-predatory activities. All these data reveal the independent origin and parallel evolution of the glycosides in different taxa of the sponges. The information concerning chemical structures, biological activities, biological role, and taxonomic distribution of the sponge glycosides is discussed.

Steroid glycosides from the roots of Marsdenia tenacissima.

Eleven undescribed glycosylated C21 steroids and nine known homologous glycosides with diverse acyl substituents, as well as their common steroid aglycone, have been obtained from the roots of Marsdenia tenacissima. Their structures were elucidated mainly by comprehensive spectroscopic analyses and comparison with previously reported analogues, with the absolute configuration assignment being supported by chemical degradation, X-ray crystallography and ECD exciton chirality method. Among them, two pairs of regioisomers were found to exist as inseparable equilibrium mixtures due to an interesting intramolecular transesterification, and nicotinoyl substitution was first reported for metabolites from the title plant. Screening of these compounds in a panel of bioassays revealed that two glycosides displayed mild inhibition against butyrylcholinesterase.

Steroid glycosides isolated from Paris polyphylla var. chinensis aerial parts and paris saponin II induces G1/S-phase MCF-7 cell cycle arrest.

In our previous research on Vietnamese medicinal plants, we found that the ethanolic extract of the aerial parts of Paris polyphylla var. chinensis exhibited cytotoxic effects in vitro in the MCF-7 human cancer cell line. Here, we used combined chromatographic separations to isolate six compounds including a new steroid glycoside, paripoloside A (3), and five known compounds, from the butanol extract of the aerial parts of P. polyphylla. We unambiguously elucidated their structures based on spectroscopic data (proton and carbon-13 nuclear magnetic resonance, heteronuclear single quantum coherence, heteronuclear multiple bond correlation, correlation spectroscopy, and high-resolution electrospray ionization mass spectroscopy data), and chemical reactions. Among the isolated compounds, paris saponin II (PSII) had the strongest cytotoxic effects against MCF-7 breast cancer cells. Interestingly, PSII significantly increased the expression of p53, p21, p27, and Bax protein levels and significantly suppressed the expression of cyclin D1 and retinoblastoma protein. These data suggest that PSII may induce G1/S phase cell cycle arrest and apoptosis pathway development in MCF-7 cells. Furthermore, the MCF-7 breast cancer cells mechanism of PSII was also investigated using molecular docking. Together, our results demonstrate that isolated compounds from P. polyphylla are promising candidates as breast cancer inhibitors.

Application of MS-Based Metabolomic Approaches in Analysis of Starfish and Sea Cucumber Bioactive Compounds.

Today, marine natural products are considered one of the main sources of compounds for drug development. Starfish and sea cucumbers are potential sources of natural products of pharmaceutical interest. Among their metabolites, polar steroids, triterpene glycosides, and polar lipids have attracted a great deal of attention; however, studying these compounds by conventional methods is challenging. The application of modern MS-based approaches can help to obtain valuable information about such compounds. This review provides an up-to-date overview of MS-based applications for starfish and sea cucumber bioactive compounds analysis. While describing most characteristic features of MS-based approaches in the context of starfish and sea cucumber metabolites, including sample preparation and MS analysis steps, the present paper mainly focuses on the application of MS-based metabolic profiling of polar steroid compounds, triterpene glycosides, and lipids. The application of MS in metabolomics studies is also outlined.

[Chemical constituents of ethnic medicine Cynanchum otophyllum].

In order to isolate and purify the reference compounds and improve the quality standard of ethnic medicine of Radix of Cynanchum otophyllum, the ethanol extracts were isolated by column chromatography onsilica gel, C18 reverse-phase silica gel, and semi-preparative HPLC. Twelve compounds were isolated and their structures were elucidated as 2,4-dihydroxy-6-methoxyphenylethanone(1), 4,6-dihydroxy-2-methoxyphenylethanone(2), p-hydroxyacetophenone(3), baishouwubenzophenone(4), 2,4-dihydroxyacetophenone(5), 2,5-dihydroxyacetophenone(6), otophylloside A(7),otophylloside B(8), caudatin-3-O-ß-D-cymaropyranosyl-(1→4)-ß-D-digitoxopyranoside(9),caudatin-3-O-ß-D-glucopyranosyl-(1→4)-ß-D-oleandropyranosyl-(1→4)-ß-D-cymaropyranosyl-(1→4)-ß-D-digitoxopyranoside(10),qingyangshengenin-3-O-ß-D-oleandropyranosyl-(1→4)-ß-D-cymaropyranoside(11),caudatin-3-O-ß-D-oleandropyranosyl-(1→4)-ß-D-cymaropyranosyl-(1→4)-ß-D-cymaropyranoside(12) on the basis of spectral analysis. Compounds 1 and 2 were isolated from the genus Cynanchum for the first time, and compounds 3-4, 9-12 were obtained from this plant for the first time.These compounds are main active components of Radix of C.otophyllum and can be used as reference substances for the quality control of this ethnic medicine.