Dihydroxyflavones Research Articles

Bioactivity of a dihydroxy flavone produced by Penicillium EU0013 against the wilt pathogen of tomato

Bioassay-guided isolation of a dihydroxy flavone from the cell extract of Penicillium EU0013 was carried out using preparative LCMS and the structure was interpreted using 1D and 2D NMR spectra. The fungus was fermented in three different nutrient media i.e. Glucose Nutrient Broth, Glucose Peptone Yeast Broth, and Yeast Extract Broth and the cell extract was obtained using organics. Comparative LCMS profiles of the fungus confirmed the enhanced production of dihydroxy flavone in GPYB media. In this study, the pathogenicity of the dihydroxy flavone is reported for the first time against Fusarium oxysporum f.sp. lycopersici, wilt causing pathogen of a tomato plant. In MIC experiments, the compound inhibited the pathogen at 80 µg mL−1. Molecular docking studies of the compound with Fol tomatinase showed five binding interactions. These docking studies may help explore dihydroxy flavones as a lead for developing new fungicides to prevent wilt disease in tomatoes.

In vitro antioxidant and anti-arthritic activity of certain dihydroxy flavones

In vitro antioxidant and anti-arthritic activity of certain dihydroxy flavones

Inhibitory Action Against Alpha Glucosidase by Selected Dihydroxy Flavones

Inhibitory Action Against Alpha Glucosidase by Selected Dihydroxy Flavones

Site-specific oxidation of flavanone and flavone by cytochrome P450 2A6 in human liver microsomes

The roles of human cytochrome P450 (P450 or CYP) 2A6 in the oxidation of flavanone [(2R)- and (2S)-enantiomers] and flavone were studied in human liver microsomes and recombinant human P450 enzymes.CYP2A6 was highly active in oxidizing flavanone to form flavone, 2′-hydroxy-, 4′-, and 6-hydroxyflavanones and in oxidizing flavone to form mono- and di-hydroxylated products, such as mono-hydroxy flavones M6, M7, and M11 and di-hydroxy flavones M3, M4, and M5.Liver microsomes prepared from human sample HH2, defective in coumarin 7-hydroxylation activity, were very inefficient in forming 2′-hydroxyflavanone from flavanone and a mono-hydroxylated product, M6, from flavone. Coumarin and anti-CYP2A6 antibodies strongly inhibited the formation of these metabolites in microsomes prepared from liver samples HH47 and 54, which were active in coumarin oxidation activities.Molecular docking analysis showed that the C2′-position of (2R)-flavanone (3.8 Å) was closer to the iron center of CYP2A6 than the C6-position (10 Å), while distances from C2′ and C6 of (2S)-flavanone to the CYP2A6 were 6.91 Å and 5.42 Å, respectively.These results suggest that CYP2A6 catalyzes site-specific oxidation of (racemic) flavanone and also flavone in human liver microsomes. CYP1A2 and CYP2B6 were also found to play significant roles in some of the oxidations of these flavonoids by human liver microsomes.

A study on antidepressant-like effect of dihydroxy flavones in mice and their mechanisms involved

Background: In the treatment of depression, drugs with a quick onset of action and high margin of safety are intensely being searched. Previous studies indicate flavonoids as a potential source for such drugs. Hence, in the present study, four dihydroxy flavones have been selected for investigation. Aims and Objectives: The aim of this study is to investigate the potential antidepressant effect and the mechanism of action of dihydroxy flavone derivatives in mice. Materials and Methods: Mice were subjected to forced swim test and tail suspension test for 6 min. The period of immobility in these animals was recorded after treatment with different doses of 3,7-dihydroxy flavone, 3,3’-dihydroxy flavone, 6,3’-dihydroxy flavone, and 5,6–dihydroxy flavone. Interacting drugs such as para chlorophenylalanine, alpha-methyl-para-tyrosine, L-arginine, and naloxone were employed to delineate the role of various mechanisms involved in the action of these dihydroxy flavones in forced swim test. Results: A dose-dependent reduction in the immobility period of mice was recorded in both forced swim test and tail suspension test for dihydroxy flavones indicating the antidepressant-like effect of these compounds. However, 6,3’-dihydroxy flavone was found to be less effective than the other three compounds. Various interacting drugs differentially modulated the reduction of immobility period produced by dihydroxy flavones in forced swim test. Monoaminergic, opioid, and nitric oxide pathways were evident in the action of dihydroxy flavones. Conclusion: The present study identified the potential antidepressant effect of a few dihydroxy flavone derivatives involving novel mechanisms.

Anti-Inflammatory Effect of Selected Dihydroxyflavones.

The mechanism of inflammation is attributed, to release of reactive oxygen species from activated neutrophils and macrophages. Over production of reactive oxygen species may result in tissue injury by damaging macromolecules. Flavones are the polyphenolic compounds with antioxidant property. This antioxidant property of flavones may have beneficial effect against inflammation. To study the anti-inflammatory effect of selected dihydroxyflavones (DHF) in albino rats. The prime objective of the present study is to identify safe and effective agents to treat inflammation from among the selected DHF group of compounds. The present study was designed to investigate the anti-inflammatory action of four selected dihydroxyflavone derivatives; 2',3'- dihydroxyflavone and 2', 4' -dihydroxyflavones, 5, 3'- dihydroxyflavone and 7, 3' dihydroxyflavone. The anti-inflammatory activity of selected DHF was studied in rats by carrageenan induced hind paw oedema method. All the selected dihydroxyflavone derivatives showed dose and time dependent inhibition of carrageenan induced paw oedema.

Anti-Inflammatory Effect of Certain Dihydroxy Flavones and the Mechanisms Involved

This study was designed to evaluate the anti-inflammatory action of four dihydroxy flavone derivatives; 3,3'- dihydroxy flavone, 5,6-dihydroxy flavone, 3,7-dihydroxy flavone and 6,3'-dihydroxy flavone and to further investigate the multiple cellular mechanisms underlying the anti-inflammatory effect of these compounds. The effect of dihydroxy flavones on acute inflammation was studied in rats employing carrageenan induced hind paw edema method. Further, the role of proinflammatory cytokines like TNF-α and IL-1β, cyclooxygenases (COX-1 and COX-2), and free radicals in the action of flavone derivatives was investigated using in vitro assays. All the four dihydroxy flavone derivatives exhibited time and dose dependent inhibition of carrageenan induced paw edema. In addition, the investigated compounds inhibited both the isoforms of cyclooxygenase and cytokines in a concentration dependent manner and also suppressed the release of reactive oxygen species. The anti-inflammatory effect of dihydroxy flavones may be through mechanisms that involve an interaction with cyclooxygenases, cytokines and reactive oxygen species.

Antinociceptive effect of certain dihydroxy flavones in mice

Objective This study was designed to evaluate the antinociceptive action of four dihydroxy flavone derivatives; 3,3′-dihydroxy flavone, 5,6-dihydroxy flavone, 3,7-dihydroxy flavone and 6,3′-dihydroxy flavone and to investigate the mechanisms involved. Materials and methods The antinociceptive effect of dihydroxy flavones was investigated in mice employing acetic acid induced abdominal constrictions, formalin-induced nociception, and hot plate assay procedures. The effects following pretreatment with naloxone, yohimbine, ondansetron, haloperidol, bicuculline and glibenclamide were also studied by acetic acid assay to reveal the involvement of opioid, adrenergic, tryptaminergic, dopaminergic, GABAergic or potassium channels respectively in the antinociceptive action of these compounds. Results Dihydroxy flavone derivatives significantly reduced the number of abdominal constrictions in acetic acid assay. The paw licking response time during both the early and late phases of formalin-induced nociception was reduced in a dose dependent manner by dihydroxy flavones treatment. A significant increase in reaction time was also evident in hot plate assay after dihydroxy flavones treatment. The antinociceptive effect of dihydroxy flavones in the acetic acid assay was significantly attenuated by pretreatment with either naloxone or bicuculline. However, pretreatment of animals with yohimbine, ondansetron, haloperidol, or glibenclamide did not alter the response. Conclusion All the four investigated dihydroxy flavones produced dose related antinociception through mechanisms that involve an interaction with opioid and GABAergic pathways.

Antinociceptive activity of certain dihydroxy flavones

Four dihydroxy flavone derivatives viz 5,3´-, 7,3´-, 2´,3´- and 2´,4´-dihydroxy flavones were evaluated for their antinociceptive response in doses ranging from 3 to 200 mg/kg (s.c). Antinociception in mice was studied employing acetic acid induced abdominal constrictions, formalin induced nociception and tail immersion assay procedures. Involvement of opioid mechanism in the antinociceptive action of dihydroxy flavones was investigated using naloxone in acetic acid assay. All the four tested dihydroxy flavones exhibited a significant, dose related antinociceptive response in these assay procedures. The inhibition of nociceptive response was more than 98% in acetic acid writhing assay and 100% in the chronic phase of formalin assay. Naloxone almost completely antagonized the antinociceptive response of the four-dihydroxy flavone compounds. In conclusion, all the four investigated dihydroxy flavones exhibited opioid mediated antinociceptive response in mice.

ChemInform Abstract: Synthesis of Trihydroxyphenacylidene Triphenylphosphoranes: A New Access to Dihydroxyflavones (Chrysine, Acacetine...).

AbstractThe phosphoranes (III) are obtained from the trihydroxyaryl ketones (I) and triphenylphosphine (II).

Syntheses of 5,6,7- and 5,7,8-trioxygenated 3',4'-dihydroxyflavones having alkoxy groups and their inhibitory activities against arachidonate 5-lipoxygenase.

Arachidonate 5-lipoxygenase plays a pivotal role in the biosynthesis of leukotrienes. Cirsiliol (3',4',5-trihydroxy-6,7-dimethoxyflavone), a selective inhibitor of the enzyme, was derivatized by introducing alkyl groups of various chain lengths at positions 5, 6, 7, and 8 of the A ring of the flavone skeleton. Modification of the positions 5 and 6 with an alkyl group of 5-10 carbons markedly decreased the IC50 values for 5-lipoxygenase inhibition to the order of 10 nM. As tested with 5- or 6-hexyloxy derivatives, a relatively selective inhibition of 5-lipoxygenase was shown. Inhibition of 12-lipoxygenase required much higher concentrations of these compounds, and cyclooxygenase was not inhibited. Modification of positions 7 and 8 did not increase the inhibitory effect of most flavone compounds.