Semi-Synthesis of Flavonoid Glycosides and Their Anti-Inflammatory and Antitumor Activities towards Triple Negative Breast Cancer.

BACKGROUND: Flavonoid glycosides are known to possess diverse bioactivities including antitumor and anti-inflammatory properties. Hesperetin is abundant in nature and can be used to synthesize bioactive flavonoids. This has the advantages of low cost, short synthetic steps, simple operation, and good yields. OBJECTIVE: In this study, we aimed to synthesize bioactive flavonoids and flavonoid glycosides from hesperetin and evaluate the antitumor and anti-inflammatory activities of these compounds. METHODS: A series of flavonoids and their derivatives were synthesized by methoxylation, oxidative dehydrogenation, benzylation, debenzylation, and deacetylation as well as using a modified peroxyacetone method and a glycoside condensation reaction. Their anti-inflammatory activities were evaluated for their inhibitory effects on nitric oxide (NO), tumor necrosis factor (TNF-α), and interleukin-6 (IL-6) production in LPS-induced RAW264.7 mouse macrophages. Their structures were characterized by HRMS, 1 H-NMR, and 13 C-NMR, and their cytotoxicity on the human triple-negative breast cancer cell (TNBC) line, SUM 149, was tested by using the MST assay. RESULTS: Most of the compounds markedly reduced NO production in LPS-stimulated murine macrophages at the tested concentrations in a dose-dependent manner. Among these, compounds 1, 7, 9, and 17 showed significant anti-inflammatory activities against NO production in LPS-induced RAW264.7 mouse macrophages. In addition, they could also reduce the release of TNF-α and IL-6 in a concentration-dependent manner. Most of the tested compounds showed remarkable anti-human TNBC activities. Compounds 1b-1m, 1, and 3 showed a certain degree of growth inhibition effect on the human TNBC cell lines and their IC50 values were all below 16.61 µM. In addition, compound 1l was the most cytotoxic with IC50 values of 1.38±0.31 µM, while the other compounds were inactive with inhibition rates <50 % at the highest concentration tested (20 µM). CONCLUSIONS: A novel series of flavonoids were synthesized from the natural flavonoid, hesperetin, including 17 new compounds. Screening tests indicated that most of these compounds reduced NO production in LPS-stimulated murine macrophages at concentrations of 15 to 60 µM, and the inhibition generally increased in a dose-dependent manner. Some compounds showed different degrees of cytotoxicity on the human TBNC cell lines, SUM 149.

Lanostane-type triterpenoids from Ganoderma applanatum and their inhibitory activities on NO production in LPS-induced BV-2 cells.

Five previously undescribed lanostane-type triterpenoids, including two triterpenoids with a rearranged side chain (applanoic acids E and F), one C21 nortriterpenoid (16,17-dehydroapplanone E), as well as two highly oxygenated lanostane triterpenoids (methyl applaniate B and applanoic acid G), were isolated from the fruiting bodies of Ganoderma applanatum (Pers.) Pat. Their structures were elucidated on the basis of spectroscopic analysis, X-ray crystallography and ECD data. Applanoic acid E, 16,17-dehydroapplanone E, and methyl applaniate B showed inhibitory effects on the release of NO by LPS-induced BV-2 cells.

[Two new flavonoid glycosides from Nervilia fordii].

Two new flavonoid glycosides were isolated from the aerial parts of Nervilia fordii by various chromatographies such as D101 macroporous resin, ODS and preparative HPLC chromatographic techniques. Their structures were elucidated as rhamnocitrin-3-O-ß-glucopyranosyl-4'-O-ß-galactosyl-(1→3)-glucopyranoside(1) and 7,3'-di-O-methylquercetin-4'-O-[ß-galactosyl-(1→3)-ß-glucopyranosyl]-3-O-ß-glucopyranoside(2) on the basis of extensive spectroscopic analyses, including 1D-, 2D-NMR, HR-ESI-MS and analytical hydrolysis.

A new labdane diterpenoid glycoside from Nervilia fordii.

To study the chemical constituents of Nervilia fordii (Hance) Schltr., various chromatographic methods were used, including D101 macroporous resin, silica gel, ODS and preparative HPLC chromatographic techniques. A new labdane diterpenoid glycoside named as nervilifordoside A was isolated from 60% EtOH extract of Nerviliafordii. The structure of compound 1 was elucidated as 12, 17-epoxy-3-hydroxy-17-methoxy-labdan-13-en-16, 15-olide 3-O-alpha-rhamnopyranosyl-(1 --> 2)-O-beta-glucopyranoside on the basis of HR-MS, 1D and 2D NMR spectroscopic data as well as chemical methods.

Five new flavonoid glycosides from Nervilia fordii.

Five new flavonoid glycosides, namely nervilifordins F-J (1-5), were isolated from the 60% EtOH extract of the aerial parts of Nervilia fordii, along with three first isolated flavonoids (7, 8, and 13) and five known flavonoids (6, 9-12). The structures of new compounds were elucidated on the basis of 1D and 2D NMR and MS studies. Their anti-inflammatory activities were tested by measuring their inhibitory effects on nitric oxide production in lipopolysaccharide-activated RAW264.7 macrophages. Compounds 2 and 5 showed interesting inhibition effects with their EC50 values of 15.15 µM and 14.80 µM, respectively.