7-hydroxyflavone and 3-hydroxyflavone

The interactions of bio-active flavonoids, 7-hydroxyflavone (7HF) and 3-hydroxyflavone (3HF) with hen egg white lysozyme (HEWL) have been established using differential spectroscopic techniques along with the help of molecular docking method. The characteristic dual fluorescence of 3HF due to the excited intramolecular state proton transfer (ESIPT) process is altered markedly upon binding with HEWL. Both the flavonoids quenched the intrinsic fluorescence of HEWL through static quenching mechanism while the binding affinity of 7HF was found to be greater than 3HF under experimental conditions. The binding constant (K

Topics: Animals; Binding Sites; Chickens; Circular Dichroism; Flavonoids; Fluorescence Resonance Energy Transfer; Hydrogen Bonding; Molecular Docking Simulation; Muramidase; Protein Binding; Protein Structure, Tertiary; Spectroscopy, Fourier Transform Infrared; Thermodynamics

Plant flavonoids are well known as antioxidants against oxidative stress induced by exposure to external pollutants. Nicotine (NIC) is one of those agents which increases renal oxidative stress, an important factor in the pathogenesis of renal epithelial injury in smokers. Although several studies had been conducted on flavonoids and oxidative stress, the mechanism of the protective pathways are not fully understood. Here, we present studies on antioxidant properties of two mono-hydroxyflavone isomers, 3-hydroxyflanove (3HF)- and 7-hydroxyflavone (7HF), against nicotine-associated oxidative stress and injury in cultured renal proximal tubule cells and correlate their antioxidant properties with their chemical structure. Our data clearly demonstrates, for the first time, that while both 3HF and 7HF protect renal cells from NIC-associated cytotoxicity, the mechanism of their action is different: 3HF elicits protective activity via the PKA/CREB/MnSOD pathway while 7HF does so via the ERK/Nrf2/HO-1 pathway. Molecular docking and dynamics simulations with two major signaling pathway proteins showed significant differences in the binding energies of 3HF (-5.67 and -7.39 kcal.mol-1) compared to 7HF (-5.41 and -8.55 kcal.mol-1) in the matrices of CREB and Keap1-Nrf2 proteins respectively, which corroborate with the observed differences in their protective properties in the renal cells. The implications of this novel explorative study is likely to promote the understanding of the mechanisms of the antioxidative functions of different flavones.

Topics: Animals; Antioxidants; Cell Line; Cyclic AMP Response Element-Binding Protein; Enzyme Activation; Flavonoids; Heme Oxygenase-1; Kidney Tubules, Proximal; Molecular Docking Simulation; Molecular Dynamics Simulation; Nicotine; Oxidative Stress; Promoter Regions, Genetic; Protein Conformation; Rats; Reactive Oxygen Species; Superoxide Dismutase

The modulation of photophysical behaviour of small organic molecules in the presence of macrocycles is one of the most interesting areas of research. In this work we reported the interaction of two biologically active molecules 3-hydroxyflavone and 7-hydroxyflavone with macrocyclic host cucurbit [7]uril in aqueous medium. To investigate the change of photophysical properties of these two flavones, we have used steady state absorption, fluorescence, time resolved fluorescence emission spectroscopy and isothermal titration calorimetric technique. It is observed that on complexation with cucurbit [7]uril, the excited state proton transfer processes in both flavones have been facilitated. Isothermal titration calorimetric method was used in order to investigate the involvement of thermodynamic parameters in complexation between flavone with cucurbit [7]uril. The changes in thermodynamic properties due to the complexation of the flavones molecules with cucurbit [7]urils help to understand about the governing parameters involved in this complexation. The inclusion of flavone molecules inside the cavity of cucurbit [7]uril molecules was studied theoretically to decipher the molecular orientation of flavones in the presence of cucurbit [7]uril. The structure of HOMO and LUMO of the complexes between cucurbit [7]uril with flavones was reported. This study will be helpful to get the knowledge about the modulation of photophysical properties of the flavones molecules on addition of macrocyclic host cucurbit [7]uril. This study will be helpful for the use of cucurbit [7]uril as a potential drug delivery system.

Topics: Binding Sites; Bridged-Ring Compounds; Calorimetry; Drug Carriers; Drug Delivery Systems; Flavonoids; Imidazoles; Molecular Structure; Spectrum Analysis

Fisetin (3,7,3',4'-tetrahydroxyflavone) and quercetin (3,5,7,3',4'-pentahydroxyflavone) are the bioactive plant flavonoids that are potentially useful therapeutic drugs for the treatment of a broad spectrum of diseases, including atherosclerosis, cardiovascular disease, obesity, hypertension, and cancer. 3-Hydroxyflavone (3HF) and 7-hydroxyflavone (7HF) are the synthetic chromophores of fisetin and quercetin. We have exploited dual luminescence properties of fisetin and quercetin along with 3-HF and 7HF to examine their efficacy of binding and compare their interactions with DNA, which is one of the macromolecular targets of flavonoids in physiological systems. Following the sequence of the human telomeric DNA 5'-d (CCCTAA-)n/(-TTAGGG)n-5', two single-stranded DNA oligonucleotides, 5'-d(C3TA2)3C3-3' and 5'-d(T2AG3)4-3', and their duplex were used as receptors to study binding by the ligands quercetin, fisetin, and their chromophores. Circular dichroism, differential absorption, UV thermal melting, and size exclusion chromatographic studies indicated the formation of unusual DNA structures (such as C4 and G4 tetraplexes) for both the C- and G-rich single-stranded DNAs. Upon binding to DNA, dramatic changes were observed in the intrinsic fluorescence behavior of the flavonoids. Molecular docking studies were performed to describe the likely binding sites for the ligands. The spectroscopic studies on flavonoid-DNA interactions described herein demonstrate a powerful approach for examining their DNA binding through exploiting the highly sensitive intrinsic fluorescence properties of the flavonoids as their own "reporter" for their interactions with macromolecular targets.

Topics: DNA; Flavonoids; Ligands; Molecular Docking Simulation; Nucleic Acid Conformation; Protons; Spectrometry, Fluorescence; Temperature

Fermentation of 3-hydroxyflavone (1) with Beauveria bassiana (ATCC 13144) yielded 3,4'-dihdroxyflavone (3), flavone 3-O-beta-D-4-O-methylglucopyranoside (4) and two minor metabolites. 7-Hydroxyflavone (2) was transformed by Nocardia species (NRRL 5646) to 7-methoxyflavone (5) whilst Aspergillus alliaceus (ATCC 10060) converted it to 4',7-dihydroxyflavone (6). Flavone 7-O-beta-D-4-O-metylglucopyranoside (7) and 4'-hydroxyflavone 7-O-beta-D-4-O-methylglucopyranoside (8) were the metabolic products of 7-hydroxyflavone (2) when fermented with Beauveria bassiana (ATCC 7159). One of the minor metabolites of 3-hydroxyflavone (1) was tentatively assigned a beta'-chalcanol structure (9). Compounds 4, 7 and 8 are reported as new compounds. Structure elucidation of the metabolites was based on spectroscopic data.

Topics: Aspergillus; Bacteria; Fermentation; Flavonoids; Magnetic Resonance Spectroscopy; Nocardia; Spectrometry, Mass, Electrospray Ionization; Spectrophotometry, Infrared

1. The aim of this investigation was to see whether 7-OH-flavone, 5-OH-flavone and 3-OH-flavone, which are present in edible vegetables, fruit and wine, are substrates or inhibitors of human liver and duodenum sulfotransferase. 2. An assay was set up to study the sulfation of 7-OH-flavone, and using this assay, it was observed that 7-OH-flavone was sulfated and the rate of sulfation (mean +/- SD) was 324 +/- 87 pmol min(-1) mg(-1) (liver) and 584 +/- 164 pmol min(-1) mg(-1) (duodenum; p < 0.0001). 3. 7-OH-flavone sulfotransferase followed Michaelis-Menten kinetics and the K(m) (mean +/- SD) was 0.2 +/- 0.04 microM (liver) and 1.1 +/- 0.3 microM (duodenum; p = 0.008). V(max) (mean +/- SD) was 392 +/- 134 pmol min(-1) mg(-1) (liver) and 815 +/- 233 pmol min(-1) mg(-1) (duodenum; p = 0.016). 4. 5-OH-flavone and 3-OH-flavone were not sulfated and were inhibitors of human liver and duodenum SULT1A1 activity and 7-OH-flavone sulfation rate. 5. The IC50 of 5-OH-flavone for SULT1A1 was 0.3 +/- 0.06 microM (liver) and 0.3 +/- 0.1 microM (duodenum; n.s.) and those of 3-OH-flavone were 1.0 +/- 0.1 microM (liver) and 1.6 +/- 0.03 microM (duodenum; p = 0.0006). 6. There was inhibition of 7-OH-flavone sulfation rate by 5-OH-flavone and 3-OH-flavone. The IC(50) of 5-OH-flavone for the sulfation rate of 7-OH-flavone was 3.5 +/- 0.5 microM (liver) and 69 +/- 18 microM (duodenum; p < 0.0001) and for 3-OH-flavone it was 18 +/- 3.4 microM (liver) and 213 +/- 47 microM (duodenum; p < 0.0001). 7. The position of the hydroxy group confers to the molecules of OH-flavones the quality of substrate or inhibitor of sulfotransferase.

Topics: Adult; Aged; Aged, 80 and over; Arylsulfotransferase; Duodenum; Enzyme Inhibitors; Female; Flavonoids; Humans; In Vitro Techniques; Kinetics; Liver; Male; Middle Aged; Substrate Specificity; Sulfates; Sulfotransferases

Because complex mixtures of plant polyphenols exert anticancer activity in animal models, we investigated whether low-molecular-weight natural phenolic compounds (2-OH-coumaric acid, 3-OH-coumaric acid, 4-OH-coumaric acid, 3-OH-flavone, 7-OH-flavone, 4-OH-benzoic acid, 3-OH-benzoic acid, and 2,3-OH-benzoic acid) affect azoxymethane (AOM)-induced aberrant crypt foci (ACF), which have been suggested to represent preneoplastic lesions, in the colon of rats. Male Fischer 344 rats were fed diets supplemented with 0.1% (wt/wt) of the different phenolic compounds, and after 2 wk they were treated twice (1 wk apart) with AOM (15 mg/kg s.c.); the dietary treatment continued until sacrifice, 7 wk after the first injection with AOM. The results showed that none of these phenolic compounds exerted chemopreventive activity on the ACF assay. On the contrary, 3-OH-flavone slightly, although significantly, increased (P < 0.05), the number of ACF per colon [157 +/- 7 and 198 +/- 14 (SE) in control and 3-OH-flavone groups, respectively, n = 10]. We also found that the number of "large" ACF was significantly increased in the group treated with 4-OH-benzoic acid. In conclusion, none of the phenolic compounds tested demonstrated a suppressive action on ACF induction by AOM.

Topics: Animals; Anticarcinogenic Agents; Azoxymethane; Colon; Colonic Neoplasms; Coumaric Acids; Diet; Flavonoids; Hydroxybenzoates; Male; Parabens; Phenols; Precancerous Conditions; Rats; Rats, Inbred F344