C-methylated Flavonoids Research Articles

New meroterpenoids and C-methylated flavonoid isolated from Baeckea frutescens.

Phytochemical investigation of the aerial parts of Baeckea frutescens resulted in the isolation of three new mono- or sesquiterpene-based meroterpenoids, frutescones S-U (1-3), and one pair of new (±)-5,7-dihydroxy-8-isobutyryl-6-methyldihydroflavonol (4). Their structures and absolute configurations were established by HR-ESI-MS, 1D and 2D NMR, and quantum chemical ECD calculation. Compound 1 exhibited inhibitory effect on NO production in LPS-activated RAW 264.7 macrophages with an IC50 value being 0.81 μmol·L-1.

Leaves of Eugenia brasiliensis Used as a Folk Medicine Contain Cyclooxygenase Enzyme and Lipid Peroxidation Inhibitory Compounds

Tea prepared from leaves of Eugenia brasiliensis has been used as a folk medicine in Brazil to alleviate inflammation and pain. In this study, tea and methanolic extract inhibited cyclooxygenase (COX-1 and -2) enzymes and lipid peroxidation (LPO). Therefore, bioassay-guided purification of methanolic extract was carried out and afforded a new lignan ( aR,8S,8'R-7,8,7’,8'-tetrahydro-8,8'-dimethyl-3,3'-dimethoxy-4,4'-dihydroxy-dibenzocyclooctadiene) and three known C-methylated flavonoids (stropopinin; demethoxymatteucinol; myrigalone G). All isolates at 37.5 μg/mL inhibited COX enzymes, similar to aspirin and ibuprofen used as controls at 108 and 12 μg/mL, respectively. Most of the isolates also showed strong LPO inhibition at 5μg/mL.

C-Methylated Flavonoid Glycosides from Pentarhizidium orientale Rhizomes and Their Inhibitory Effects on the H1N1 Influenza Virus.

Thirteen C-methylated flavonoid glycosides (1-13), along with 15 previously known flavonoids (14-28), were isolated from rhizomes of Pentarhizidium orientale. Among these compounds, matteuorienates D-K (1-8) were obtained as analogues of matteuorienates A-C (14-16), which contain a characteristic 3-hydroxy-3-methylglutaryl (HMG) moiety. The structures of 1-13 were characterized by spectroscopic analysis and chemical derivatization. The isolates were evaluated for their antiviral activities against influenza virus (H1N1), with compounds 21, 22, 23, 25, and 26 showing inhibitory effects (IC50 of 23.9-30.3 μM) against neuraminidases.

New C-methylated flavonoids and α-pyrone derivative from roots of Talinum triangulare growing in Nigeria

The first chemical examination of roots of the traditionally used medicinal plant Talinum triangulare (Portulacaceae) from Nigeria led to the isolation of two new C-methylated flavonoids, 5,6-dimethoxy-7-hydroxy-8-methyl-flavone (1), 5,6-dimethoxy-8-methyl-2-phenyl-7H-1-benzopyran-7-one (2), and one new α-pyrone derivative, 4-methoxy-6-(2-hydroxy-4-phenylbutyl)-2H-pyran-2-one (3), along with thirteen known compounds, including nine amides (4–12), indole-3-carboxylic acid (13), p-hydroxy benzoic acid (14), and two steroids (15–16). Their structures were elucidated by extensive spectroscopic measurements including 1D, 2D NMR, MS, and by comparison with the literature. All isolated compounds were screened for their cytotoxic and antifungal activities. However, none of them showed significant activity.

Antiestrogenic and anti-HER2 activities of allspice (Pimenta dioica L., Myrtaceae) extracts in MCF-7 and SK-BR3 breast cancer cells

Human epidermal growth factor 2 (HER2) is a trans-membrane tyrosine kinase that is over expressed in 20% of breast cancers. Overexpression of HER2 has been linked to tumor proliferation and poor prognosis. Numerous studies have focused on targeting HER2 for breast cancer treatment. The leaves of Pimenta dioica (L.) Merr. (Myrtaceae), commonly known as allspice, are used in Costa Rican traditional medicine for women's health. A MeOH extract of allspice leaves collected in Costa Rica, inhibited the growth of MCF-7 (ER+, low HER2) cell proliferation with IC50 of 50 µg/ml, but were more active in SK-Br3 (ER-, high HER2) cells with an IC50 of 12.5µg/ml. In a panel of fifteen receptor tyrosine kinases (RTKs), the extract and partition inhibited two erbB RTKs, namely EGFR (HER1) and HER2 RTKs. Chromatographic separation of the EtOAc partition on a 2L C18 reversed phase silica gel column with methanol/water afforded 20 fractions. Using a high-throughput 96-well HER2 assay, the active fraction was determine to be a 50% methanol/water fraction, which also inhibited the activity of HER2 RTK. Two C-methylated flavonoids, (being new 2-phenoxychromones) were the most active with an IC50 of 1 and 5.1 µg/ml, respectively. Further preliminary data demonstrated that the 50% MeOH fraction of allspice down-regulated the expression of the HER-2 receptor protein in Western blotting and using qPCR the fraction also down-regulated the expression of the HER2 mRNA in SK-Br3 cells.

C-methylated flavonoids from Pisonia grandis roots

Five new C-methylated flavonoids (1–5) together with seven known compounds have been isolated after chromatographic separation of the hexane and CH2Cl2 extracts of the roots of Pisonia grandis (Nyctaginaceae). Structural identification of the new compounds was accomplished by spectroscopic methods. The radical scavenging and antimicrobial properties of the isolates were investigated.

Diplomorphanins A and B: New <i>C</i>-Methyl Flavonoids from <i>Diplomorpha canescens</i>

Two new C-methyl flavonoids, diplomorphanins A (1) and B (2) were isolated from the aerial parts of Diplomorpha canescens (MEISN.) C. A. MEYER along with a known compound, farrerol 7-O-β-D-glucopyranoside (3). Structures of these compounds were determined on the basis of spectroscopic data.

ChemInform Abstract: Flavonoids from the Aerial Parts of Diplomorpha canescens

Abstractisolation and structure of two new C‐methyl flavonoids (I)

C-Methylated Flavonoids from Cleistocalyx operculatus and Their Inhibitory Effects on Novel Influenza A (H1N1) Neuraminidase

As part of an ongoing study focused on the discovery of anti-influenza agents from plants, four new (1-4) and 10 known (5-14) C-methylated flavonoids were isolated from a methanol extract of Cleistocalyx operculatus buds using an influenza H1N1 neuraminidase inhibition assay. Compounds 4, 7, 8, and 14, with a chalcone skeleton, showed significant inhibitory effects on the viral neuraminidases from two influenza viral strains, H1N1 and H9N2. Compound 4 showed the strongest inhibitory activity against the neuraminidases from novel influenza H1N1 (WT) and oseltamivir-resistant novel H1N1 (H274Y mutant) expressed in 293T cells with IC50 values of 8.15 ± 1.05 and 3.31 ± 1.34 μM, respectively. Compounds 4, 7, 8, and 14 behaved as noncompetitive inhibitors in the kinetic studies. These results indicate that C-methylated flavonoids from C. operculatus have the potential to be developed as neuraminidase inhibitors for novel influenza H1N1.

Two Prenylated and C-Methylated Flavonoids fromTripterygium wilfordii

Two unusual prenylated and C-methylated flavanones, (±)-5,4'-dihydroxy-2'-methoxy-6',6''- dimethypyrano-(2'',3'':7,8)-6-methyflavanone ( 1) and (2 S)-5,7,4'-trihydroxy-2'-methoxy-8,5'- di(3-methyl-2-butenyl)-6-methyflavanone ( 2), and 10 known compounds were isolated from the stems and roots of TRIPTERYGIUM WILFORDII. Their structures were elucidated based on spectroscopic analyses including 1- and 2-D NMR, HR-ESI-MS, CD, and x-ray crystallography. The anti-inflammatory, antiproliferative, and antibacterial activities of compounds 1 and 2 were investigated. Compound 2 had an inhibitory effect on lipopolysaccharides (LPS)-triggered RAW cell nitric oxide (NO) production, with an IC (50) value of 15.0 ± 0.7 µM. Both compounds showed moderate antiproliferative activity against the tumor cell lines HT-29 and ZR-75-1.

Two Prenylated and C-methylated Flavonoids from Tripterygium wilfordii Hook. F. (Celastraceae)

Two Prenylated and C-methylated Flavonoids from Tripterygium wilfordii Hook. F. (Celastraceae)

Flavonoids from the Aerial Parts of Diplomorpha canescens

Two new C-methyl flavonoids, (2R,3S)-6,8-di-C-methyldihydrokaempferol (1) and (2R,3R)-6,8-di-C-methyldihydrokaempferol (2) were isolated from the aerial parts of Diplomorpha canescens (MEISN.) C. A. MEYER along with eleven known flavonoids such as genkwanin (3), rhamnocitrin 3-O-beta-D-glucopyranoside (4), genkwanin 5-O-beta-D-glucopyranoside (5), apigenin (6), kaempferol (7), kaempferol 3-O-beta-D-glucopyranoside (8), rhamnetin 3-O-beta-D-glucopyranoside (9), luteolin (10), quercetin (11), quercetin 3-O-beta-D-glucopyranoside (12) and genkwanin 5-O-primeveroside (13). Structures of these compounds were elucidated on the basis of spectroscopic data.

Spasmolytic Flavonoids from Syzygium samarangense (Blume) Merr. & L.M. Perry

The hexane extract of Syzygium samarangense (Ss.Hex) dose-dependently (10-1000 microg/ ml) relaxed the spontaneously contracting isolated rabbit jejunum. Four rare C-methylated flavonoids with a chalcone and a flavanone skeleton were isolated from Ss.Hex and were subsequently tested for spasmolytic activity. All flavonoids, identified as 2'-hydroxy-4',6'-dimethoxy-3'-methylchalcone (1), 2',4'-dihydroxy-6'-methoxy-3',5'-dimethylchalcone (2), 2',4'-dihydroxy-6'-methoxy-3'-methylchalcone (3), and 7-hydroxy-5-methoxy-6,8-dimethyl-flavanone (4), showed dose-dependent spasmolytic activity in the rabbit jejunum with IC50 values of 148.3 +/- 69.4, 77.2 +/- 43.5, 142.4 +/- 58.6 and 178.5 +/- 37.5 microg/ml (mean +/- SEM), respectively. The dihydrochalcone derivative of compound 1, 2'-hydroxy-4',6'-dimethoxy-3'-methyldihydrochalcone (5), when tested for spasmolytic activity, did not significantly relax the smooth muscle relative to the other compounds. Verapamil, a standard spasmolytic, has an IC50 value of 0.16 +/- 0.04 microg/ml. This is the first report of the relaxant activity of chalcones, specifically of compounds 1-3.

C-methylated flavonoids from the roots of Piper carniconnectivum C.DC. (Piperaceae)

C-methylated flavonoids from the roots of Piper carniconnectivum C.DC. (Piperaceae)

Antimicrobial constituents from goldenseal (the Rhizomes of Hydrastis canadensis) against selected oral pathogens.

Two new C-methyl flavonoids, 6,8-di- C-methylluteolin 7-methyl ether (1) and 6- C-methylluteolin 7-methyl ether (2), were isolated from a commercially available sample of the roots of Hydrastis canadensis, along with seven known compounds, berberine (3), beta-hydrastine (4), canadine (5), canadaline (6), isocorypalmine (7), canadinic acid (8), and beta-sitosterol 3- O-beta- D-glucoside (9). The structures of the new compounds 1 and 2 were elucidated on the basis of their spectral data including 1D and 2D NMR techniques. Of these isolates, berberine (3) and, to a lesser extent, 1 and 2, showed antimicrobial activity when evaluated against the oral pathogens Streptococcus mutans and Fusobacterium nucleatum. Berberine (3) exhibited an additive antimicrobial effect when tested against S. mutans in combination with 1.

A new C-methylated flavonoid glycoside from Pinus densiflora

A new C-methyl flavonol glycoside, 5,7,8,4′-tetrahydroxy-3-methoxy-6-methylflavone 8- O-β- d-glucopyranoside ( 1), has been isolated from the needles of Pinus densiflora, together with kaempferol 3- O-β-(6″-acetyl)-galactopyranoside.

C-Methyl-flavonoids from the leaf waxes of some Myrtaceae

The thin waxy coatings on leaves of nine species of Callistemon, two of Melaleuca and one species of Metrosideros, have been studied for the occurrence of leaf surface flavonoids. The Callistemon species and Metrosideros robusta exhibit only C-methylated flavonoids, while O-methyl flavonoids were detected in Melaleuca huegelii. The new natural C-methyl flavonol, 5,7-dihydroxy-3,8,4′-trimethoxy-6-C-methylflavone, was isolated from Metrosideros robusta. The leaf wax of Callistemon coccineus contains the novel C-methylflavonoid, 5,4′-dihydroxy-8-C-methyl-7-methoxy flavanone.

Uncoupling of respiration and inhibition of ATP synthesis in mitochondria by C-methylated flavonoids from Myrica gale L.

The uncoupling activity of seven C-methylated flavonoids from the fruits of Myrica gale L. was studied. Myrigalone A, B and G (MyA, MyB and MyG) uncoupled the oxidative phosphorylation in rat liver mitochondria. MyA was most potent, at 45 μM causing an increase of 87±8 natoms O/min/mg in the state 4 respiration rate, which is more than twice the effect of 2,4-dinitrophenol (DNP). MyG was slightly less active than MyA, but its activity decreased from 45 to 90 μM. MyB was approximately equipotent with DNP. Myrigalone D and H were weak uncouplers, whereas myrigalone E and angoletin were inactive. The uncoupling activity of MyA, MyB and MyG was accompanied by an inhibitory effect on the ATP synthesis. The inhibition caused by MyA at 45 μM was about 70%. Whereas the effect of MyA or MyB was nearly constant throughout the incubation period, the effect of MyG had almost vanished after 15 min. The uncoupling activity of the myrigalones does not seem to be related to their antioxidative properties.

C-Methyl Flavones from the Leaf Wax of Leptospermum laevigatum (Myrtaceae)

Abstract Flavonoid aglycones were detected as minor constituents of the leaf wax of the Myrtaceae Leptosperm um laevigatum. They belong to the rarely encountered C-methyl flavonoids. One of them is a new natural product, 5-hydroxy-3,7,3′,4′-tetramethoxy-6-C-methyl flavone.

Five new C-methyl flavonoids, the potent aldose reductase inhibitors from Matteuccia orientalis Trev.

Five new compounds, matteuorien, matteuorienin, and matteuorienate A (7), B (8), and C (9) were isolated together with five known compounds from the MeOH extract of the rhizome of Matteuccia orientalis Trev. The structures of these compounds were determined by the use of spectroscopic methods including two dimensional (2D)-NMR experiments and chemical methods, except for the configuration at the C-3"' of matteuorienate A (7), B (8), and C (9). Among them, matteuorienate A, B, and C showed very strong aldose reductase inhibitory activity. A structure-activity relationship study showed that a carboxyl group played an important part in aldose reductase inhibitory activity in these three compounds.