Trimethoxy Flavone Research Articles

ChemInform Abstract: Two New Flavones from Inula grantioides.

Two new flavones grantionin 1 and grantioidinin 2 have been isolated from Inula grantioides and their structures were determined as 7-hydroxy-6,3′,5′-trimethoxy flavone 1 and 5-hydroxy-3,6,7,8,2′,5′-hexamethoxy flavone 2 along with a known dinorsequiterpene pluchidione 3.

Molecular interaction studies of trimethoxy flavone with human serum albumin.

BackgroundHuman serum albumin (HSA) is the most abundant protein in blood plasma, having high affinity binding sites for several endogenous and exogenous compounds. Trimethoxy flavone (TMF) is a naturally occurring flavone isolated from Andrographis viscosula and used in the treatment of dyspepsia, influenza, malaria, respiratory functions and as an astringent and antidote for poisonous stings of some insects.Methodology/Principal FindingsThe main aim of the experiment was to examine the interaction between TMF and HSA at physiological conditions. Upon addition of TMF to HSA, the fluorescence emission was quenched and the binding constant of TMF with HSA was found to be KTMF = 1.0±0.01×103 M−1, which corresponds to −5.4 kcal M−1 of free energy. Micro-TOF Q mass spectrometry results showed a mass increase of from 66,513 Da (free HSA) to 66,823 Da (HAS +Drug), indicating the strong binding of TMF with HSA resulting in decrease of fluorescence. The HSA conformation was altered upon binding of TMF to HSA with decrease in α-helix and an increase in β-sheets and random coils suggesting partial unfolding of protein secondary structure. Molecular docking experiments found that TMF binds strongly with HSA at IIIA domain of hydrophobic pocket with hydrogen bond and hydrophobic interactions. Among which two hydrogen bonds are formed between O (19) of TMF to Arg 410, Tyr 411 and another one from O (7) of TMF to Asn 391, with bond distance of 2.1 Å, 3.6 Å and 2.6 Å, respectively.Conclusions/SignificanceIn view of the evidence presented, it is imperative to assign a greater role of HSA's as a carrier molecule for many drugs to understand the interactions of HSA with TMF will be pivotal in the design of new TMF-inspired drugs.

Antagonism of Aryl Hydrocarbon Receptor Signaling by 6,2′,4′-Trimethoxyflavone

The aryl hydrocarbon receptor (AHR) is regarded as an important homeostatic transcriptional regulator within physiological and pathophysiological processes, including xenobiotic metabolism, endocrine function, immunity, and cancer. Agonist activation of the AHR is considered deleterious based on toxicological evidence obtained with environmental pollutants, which mediate toxic effects through AHR. However, a multitude of plant-derived constituents, e.g., polyphenols that exhibit beneficial properties, have also been described as ligands for the AHR. It is conceivable that some of the positive aspects of such compounds can be attributed to suppression of AHR activity through antagonism. Therefore, we conducted a dioxin response element reporter-based screen to assess the AHR activity associated with a range of flavonoid compounds. Our screen identified two flavonoids (5-methoxyflavone and 7,4'-dimethoxyisoflavone) with previously unidentified AHR agonist potential. In addition, we have identified and characterized 6,2',4'-trimethoxyflavone (TMF) as an AHR ligand that possesses the characteristics of an antagonist having the capacity to compete with agonists, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin and benzo[a]pyrene, thus effectively inhibiting AHR-mediated transactivation of a heterologous reporter and endogenous targets, e.g., CYP1A1, independent of cell lineage or species. Furthermore, TMF displays superior action by virtue of having no partial agonist activity, in contrast to other documented antagonists, e.g., alpha-napthoflavone, which are partial weak agonists. TMF also exhibits no species or promoter dependence with regard to AHR antagonism. TMF therefore represents an improved tool allowing for more precise dissection of AHR function in the absence of any conflicting agonist activity.

Activation of the CFTR Cl- Channel by Trimethoxyflavone in vitro and in vivo

The flavone apigenin has been previously selected as a potent pharmacological activator of the CFTR Cl^- channel, however, its utility for the activation of CFTR in vivo is expected to be limited because flavonoids are readily metabolized. We therefore investigated the poorly metabolizable methylether of apigenin, 5,7,4’-trimethoxyflavone (TMF) as a CFTR activator using transepithelial short-circuit current measurements, whole cell and single cell patch clamp techniques, and nasal potential difference (PD) measurements. Transepithelial Cl^- secretion by Calu-3 epithelia was stimulated by TMF with a halfmaximal concentration of 64±5 μM to 55±15% of maximal currents achieved by subsequent addition of cAMP agonist forskolin (10 μM). In forskolin-prestimulated tissues, TMF showed small effects and stimulated Cl^- secretion by an additional 6%. Single channel and whole cell patch clamp techniques were used to verify these effects and identify CFTR as the target of TMF. TMF increased the open probability of silent CFTR (to 0.31±0.06) but showed small effects once CFTR had been prestimulated with forskolin. In nasal PD measurements in humans, perfusion of TMF onto the nasal mucosa activated nasal PD by -9.5±1.1 mV, which was 69% of the effect of TMF+isoproterenol (-13.8±3.9 mV). These data show that TMF is an activator of CFTR in both in vitro and in vivo assays that targets mainly the unstimulated CFTR.

Enhancement of paclitaxel transport and cytotoxicity by 7,3’,4’-trimethoxyflavone, a P-glycoprotein inhibitor

Paclitaxel has problems with respect to bioavailability and resistance. The aim of this study was to select a P-glycoprotein (Pgp)- inhibitory flavonoid to enhance paclitaxel bioavailability in the Caco-2 cell monolayer. Cytotoxicity and chemosensitization were determined using MTT assay. Paclitaxel transport was examined in the Caco-2 cell monolayer, which mimics the intestinal barrier. Paclitaxel concentrations were quantitated by HPLC assay using the internal standard method. Chemosensitizing indeces of 7,3',4'-trimethoxyflavone (TMF) and verapamil was > 333 and 152, respectively. The basolateral (BL)- to-apical (AP) transport of paclitaxel was more than 10-fold greater than its AP-to-BL transport. TMF and verapamil increased the AP-to-BL transport of paclitaxel but decreased its BL-to-AP transport in a concentration-dependent manner. The net absorptive effect of 50 microM TMF on paclitaxel transport was comparable to that of 50 muM verapamil. In addition, AP loading of TMF increased the paclitaxel sensitivity of paclitaxel-resistant SK-MES-1/PT4000 cells overexpressing Pgp on the BL side. These results indicate that TMF with low toxicity can be used as an enhancer of oral paclitaxel bioavailability and as a Pgp inhibitor.

Phytochemical and antimicrobial studies on Artemisia monosperma

The use of natural products with therapeutic properties is as ancient as human civilization and, for a long time, mineral, plant and animal products were the main source of drugs. Herbal medicines used to treat many diseases including several infections. The present study deals with the isolation and identification of flavonoids from the aerial part of Artemisia monosperma and evaluation of the antimicrobial effects of a methanol-water (70:30) extract. This extract of A. monosperma was subjected to repeated chromatography on polyamide, cellulose and Sephadex LH-20 resulting in, quercetin 3-O-β-glucopyranoside, quercetin 5-O- β -glucopyranoside, isorhamnetin 5- O-β-glucopyranoside, 5,4′-dihydroxy 6,7-dimethoxy flavone, 5,4-dihydroxy 6,7, 3′-trimethoxy flavone, quercetin and isorhamnetin. The structures of the isolated compounds was elucidated on the basis of spectral analysis. The hydroalcoholic extract of the aerial part of A. monosperma exhibited variable degrees of antimicrobial activity (diffusion method). The extract shows a moderate activity against Escherichia coli and Bacillus cereus (20mm diameter) and low activity against Bacillus subtilis (16mm diameter) compared with that exerted by antibiotics (MIC,1.020–3.05mg/ml). It was found inactive against Staphylococcus aureus and Streptococcus pyogens [1,2].

Cytotoxic phenolic constituents ofAcer tegmentosum maxim

The chromatographic separation of the MeOH extract from the twigs of Acer tegmentosum led to the isolation of ten phenolic compounds. The structures of these compounds were determined using spectroscopic methods as 3,7,3',4'-tetramethyl-quercetin (1), 5,3'-dihydroxy-3,7,4'-trimethoxy flavone (2), 2,6-dimethoxy-p-hydroquinone (3), (-)-catechin (4), morin-3-O-alpha-L-lyxoside (5), p-hydroxy phenylethyl-O-beta-D-glucopyranoside (6), 3,5-dimethoxy-4-hydroxy phenyl-1-O-beta-D-glucoside (7), fraxin (8), 3,5-dimethoxy-benzyl alcohol 4-O-beta-D-glucopyranoside (9) and 4-(2,3-dihydroxy propyl)-2,6-dimethoxy phenyl beta-D-glucopyranoside (10). The compounds were examined for their cytotoxic activity against five cancer cell lines. Compound 3 exhibited good cytotoxic activity against five human cancer cell lines with ED50 values ranging from 1.32 to 3.85 microM.

Three new diterpenes and the biological activity of different extracts of Jasonia montana

Three new diterpenes, namely jasonin-a (1), jasonin-b (2), and jasonin-c (3) were isolated from the aerial parts of Jasonia montana (Asteraceae). Their structures were elucidated on the basis of spectral data as [(1E)-2-((2S)-1,2,5-trimethylbicyclo[3.2.1]octan-8-yl)vinyl] benzene-3-carboxylic acid (1), [3-((2S, 5S)-1,2, 5-trimethylcycloheptanyl)propyl]benzene-3-carboxylic acid (2), and [(1E)-3-((7R)-1,7-dimethy-4-methylenecycloheptanyl)prop-1-enyl] benzene-3-carboxylic acid (3). In addition, the previously reported 5,7,3′-trihydroxy-3,6,4′-trimethoxy flavone designated as centaureidin (4), was also isolated and characterized from this source. The different extracts of the plant were also screened for hypoglycemic, antidiabetic, and antimicrobial activities, wherein the petroleum ether and ethanolic extracts exhibited hypoglycemic and antidiabetic activity, and the petroleum ether and chloroform extracts showed antimicrobial activity.

Flavonoids from Three Ethiopian Species of Premna

Two novel hepta-oxygenated flavonols have been isolated from the aerial parts of Premna oligotricha and identified, primarily on the basis of N M R spectroscopy, as 3,5,5'-trihydroxy- 6,7,3',4'-tetram ethoxyflavone (2) and 3,5,7,5'-tetrahydroxy-6,3',4'-trim ethoxyflavone (3). Known flavonoids, with lower levels of oxygenation were obtained from two other Premna species, P. schimperi and P. recinosa.

Two New Flavones from Inula grantioides

Two new flavones grantionin 1 and grantioidinin 2 have been isolated from Inula grantioides and their structures were determined as 7-hydroxy-6,3′,5′-trimethoxy flavone 1 and 5-hydroxy-3,6,7,8,2′,5′-hexamethoxy flavone 2 along with a known dinorsequiterpene pluchidione 3.

New Frond Exudate Flavonoids From Cheilanthoid Ferns

A series of new flavonoid aglycones have been identified in the frond exudates of the fern Cheilanthes argentea, in five species of Notholaena, in Pityrogramma triangularis, and in Platyzoma microphylla. These aglycones comprise several rare flavonoids and five novel natural products: 5,7,8-trihydroxy-3-methoxy-6-methyl flavone, 3,5,2′-trihydroxy-7,8,4′-trimethoxy flavone, 5,2′-dihydroxy-3,7,8-trimethoxy flavone, 5,7,4′-trihydroxy-2′-methoxy flavanone, and 3,5,4′-trihydroxy-6,7,8-trimethoxy flavone. The novel flavonoids were characterized by their N M R spectral data

Phytochemical Investigation of Cassia laevigata Pods, Part I

From the pods of Cassia laevigata three flavonoids, 3,5,3'–trihydroxy–7,4'–dimethoxy flavone–3–0–β–D(+) galactopyranoside, 3,5–dihydroxy–7,3',4'–trimethoxy flavone–3–O–β–D(+) galactosyl–O–β–D(+) galactopyranoside and quercetin, have been isolated and studied.