Hydroxyflavone Derivatives Research Articles

Synthesis and in vitro biochemical properties, DNA binding and DNA cleavage ability of copper complexes of hydroxyflavone derivatives of novel organosulfur compounds as therapeutic agent

Novel and synthetically essential flavonoids compounds containing the organosulfur moiety from Schiff bases, as well as their copper complexes, were synthesized from chrysin and 2-(phenylthio)aniline. These complexes were characterized using elemental analysis, mass spectrometry, electronic absorption spectroscopy, IR, 1H, and 13C NMR spectroscopy techniques. All the Cu(II) complexes exhibit square planar geometry. The in vitro antimicrobial activities of the investigated compounds were tested against the bacterial species, Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Staphylococcus epidermidis, and Klebsiella pneumoniae and fungal species, Aspergillus niger, Fusarium solani, Culvularia lunata, Rhizoctonia bataicola, and Candida albicans by serial dilution method. The DNA binding and DNA cleavage properties of copper complexes were studied. Free radical scavenging, superoxide dismutase, glutathione peroxidase, and antioxidant activities of the copper complexes have also been studied. In addition, using the egg albumin process, the in vitro anti-inflammatory efficacy of metal chelates was examined. Anti-tuberculosis and α-glucosidase inhibition activity were carried out from the prepared metal complexes. The flavonoid compounds containing the organosulfur moiety of Cu(II) complexes (1–8) exhibited better therapeutic agent.

Biological properties of ruthenium(II)/(III) complexes with flavonoids as ligands

• Overview of ruthenium(II)/(III) complexes with flavone derivatives. • Therapeutic properties of flavonoids and biological properties of Ru complexes with flavonoids. • Chemistry of Ru(η 6 -arene) complexes of flavonoids. • Interaction between biological targets and flavonoids and their ruthenium(II)/(III) complexes. This review highlights the progress in the development of ruthenium(II)/(III) complexes with flavone derivatives as potential therapeutic agents. We focused on natural hydroxyflavone derivatives and their synthetic amino analogues as ligands in ruthenium(II)/(III) complexes which demonstrate antimicrobial, antitumor activity and/or enzyme inhibition. Some enzymes targeted by flavone derivatives are important for the development and progression of cancer cells which underpins the design concept for the Ru complexes as multitargeted compounds consisting of a bioactive ligand and a ruthenium center.

Artificial light-harvesting supramolecular assemblies with controllable fluorescence intensity formed by cyclodextrin-based host-gost complexation

In the present work, we have designed and synthesized an amphiphilic hydroxyflavone derivative (HFD) with a hydrophilic side chain, which can self-assembly into spherical aggregates with the diameter at about 100 nm in aqueous solution. Meanwhile, HFD can interact with cyclodextrins (CDs) with different cavity sizes through host-guest interaction, which also exhibited different fluorescence intensity in aqueous solution. α-CD has no obvious effect on the fluorescence and self-assembled structures because the cavity of α-CD is too small to encapsulate HFD into its cavity. However, β-CD and γ-CD can form 1: 1 and 1: 2 complexes with HFD in aqueous solution, which lead to enhanced and reduced fluorescence intensity of HFD, respectively. Moreover, after addition of β-CD and γ-CD, HFD can self-assembly into aggregated nanoparticles and spherical aggregates with the diameter at about 200 nm, respectively. More interestingly, artificial light-harvesting systems can be constructed by using HFD and HFD with CDs as energy donors with gradual addition of sulfo-cyanine5 carboxylic acid (Cy5) as energy acceptors in aqueous solution.

3’, 4’-Dihydroxyflavone enhances all-<i>trans</i> retinoic acid-induced superoxide-generating activity through up-regulating transcription of gp91-phox in human monoblastic U937 cells, as opposed to flavone and other hydroxyflavone derivatives

3’, 4’-Dihydroxyflavone enhances all-<i>trans</i> retinoic acid-induced superoxide-generating activity through up-regulating transcription of gp91-phox in human monoblastic U937 cells, as opposed to flavone and other hydroxyflavone derivatives

Designing and Synthesis of Flavonoids Derivatives and Screening of their Antioxidant Activity

The flavonoids present in red wine were responsible this low cardiovascular mortality rate. Epidemiologic studies further suggest that dietary flavonoids are useful to control and protect the CHD. The flavonoids are yellow color substance (pigments) and the name given on the basis of Latin term Flavus which means yellow color. Flavonoids are derivatives of benzo-pyrone. Banzopyrone is a group of heterocyclic aromatic oxygen containing compounds. Finely powdered zinc chloride (8.25) was dissolved in glacial acetic acid (18ml) by heating on sand bath then dry resorcinol (appx.5.5 gm) was added with continuous stirring to the mixture at 1400C. Antioxidant Screening by hydrogen peroxide scavenging assays. Hydrogen peroxide solution (40 mini moles) was prepared with standard phosphate buffer of pH 7.4. Different concentration of the compound stock solution and 4ml distilled water was added to 0.6 ml of hydrogen peroxide solution. UV absorbance was determined at the wavelength of 230 nm after 10 min with a blank solution containing phosphate buffer without H2O2. Take 4 ml different concentration of sample solution and 1ml sodium nitroprusside solution, added and incubated for 2.5 hrs at 370C. After incubation baseline was taken with methanol and 1ml sodium nitroprusside solution as blank solution. Griess reagent and methanol was added immediately before recording of readings. The readings were recorded at 546nm wavelenth. In the series of synthesized and evaluated compounds of Flavanoid electron withdrawing group at position four shows good activity. 2,3-dihydroflavan-3-ol derivatives showed lower activity than that of 3- hydroxyflavone derivatives. The 4-oxo (keto double bond at position 4 of the C ring), especially in association with the J2-J3 double bond, increases scavenger activity by delocalizing electrons, 3-hydroxy group on the C ring generates an extremely active scavenger; the combination of J2-J3 double bond,3-hydroxy group and 4-oxo group appears to be the best combination for potent antioxidant activity.
 Keywords: Flavonoids, Antioxidant activity, Hydrogen peroxide scavenging, free radicals

A two-channel mechanism for the asymmetric excited-state intramolecular double proton transfer in a hydroxyflavone derivative

The excited-state proton transfer (ESPT) mechanism of 3,7-dihydroxy-2-phenyl-6-acetyl-4H-chromen-4-one (DPACO) fluorophore was studied by the density functional theory (DFT) and time-dependent density functional theory (TD-DFT) with CAM-B3LYP functional and 6–31 +G(d,p) basis set. The computation levels are reliable as evidenced by the accordance between theory and experiment. In the ground state of DPACO, two intramolecular hydrogen bonds were formed. After photo-excitation, the electron density redistributions provide the driving force for hydrogen-bonding strengthening and ESPT. The constructed potential energy surfaces (PESs) along proton transfer (PT) coordinates indicate that two PT channels exist in the excited state. Among various PT tautomers, T4*is theoretically assigned as the main fluorescence emitter, while the low fluorescence quantum yield possibly correlate with the accelerated internal conversion pathway in the PT tautomer T6*.

Synthesis and biological evaluation of acyl derivatives of hydroxyflavones as potent antiproliferative agents against drug resistance cell lines.

The synthesis of hydroxyflavone derivatives is described. The acyl derivatives of 3-, 6-, 7-hydroxyflavones (compounds 2, 4, 6, respectively) and chrysin (5,7-dihydroxyflavone, 7) were obtained in high yields and evaluated in vitro for their cytotoxic activity against several cancer cell lines of different origin: MCF-7 (breast cancer), A549 (nonsmall cell lung cancer), MES-SA (uterine sarcoma), LoVo (colon cancer), drug-resistant human cancer cells (MES-SA/DX5, LoVo/DX) and also towards non-cancer cell line MCF-10A (normal breast epithelial cells). The flavones modified with acyl group showed higher antiproliferative activity than free hydroxyflavones. The highest activity was noted for 3-acetoxyflavone (2), which proved active against LoVo, LoVo/DX, and MES-SA cell lines (IC50 from 4.7 μM to 7.8 μM, respectively). The highest ability to overcome the barrier of resistance (resistance index=0.82) against the drug-resistant MES-SA/DX5 cells compared to the parental drug-sensitive MES-SA cell line was found for 7-acetoxyflavone (6).

Synthesis, characterization and pharmacological studies of copper complexes of flavone derivatives as potential anti-tuberculosis agents

Novel series of different hydroxyflavone derivatives and their copper complexes were synthesized. They were characterized using analytical and spectral techniques. The superoxide dismutase (SOD) mimetic activity of the synthesized complexes demonstrated that copper complex of L10 has promising SOD-mimetic activity than other ligands & complexes. The in vitro antimicrobial activities of the synthesized compounds were tested against the bacterial species and fungal species. The DNA binding properties of copper complexes were studied using cyclic voltametry and electronic absorption techniques. Anti-tuberculosis activity was also performed. The effective complexes was subjected to antimycobacterial activity using MABA method and summarized. The antimycobacterial activity of copper complexes have been evaluated and discussed.

Novel Copper-Based Therapeutic Agent for Anti-Inflammatory: Synthesis, Characterization, and Biochemical Activities of Copper(II) Complexes of Hydroxyflavone Schiff Bases

Four hydroxyflavone derivatives have been synthesized with the aim of obtaining a good model of superoxide dismutase. Better to mimic the natural metalloenzyme, copper complexes have been designed. The Cu(II) complexes of general formulae, [CuL] where L = 5-hydroxyflavone-o-phenylenediamine (L¹H₂)/m-phenylenediamine (L²H₂) and 3-hydroxyflavone-o-phenylenediamine (L³H₂)/m-phenylenediamine (L⁴H₂) have been synthesized. The structural features have been determined from their analytical and spectral data. All the Cu(II) complexes exhibit square planar geometry. Redox behavior of copper complexes was studied and the present ligand systems stabilize the unusual oxidation state of the copper ion during electrolysis. The in vitro antimicrobial activities of the investigated compounds were tested against the bacterial species Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Proteus vulgaris, and Pseudomonas aeruginosa and fungal species Aspergillus niger, Rhizopus stolonifer, Aspergillus flavus, Rhizoctonia bataicola, and Candida albicans. Superoxide dismutase and anti-inflammatory activities of the copper complexes have also been measured and discussed.

Copper(II) complexes of hydroxyflavone derivatives as potential bioactive molecule to combat antioxidants: synthesis, characterization and pharmacological activities

AbstractA variety of novel copper complexes were synthesized and characterized of the formulae [Cu(L1)(OAc)], [CuL2(H2O)], [CuL3(H2O)], [CuL4(OAc)], [CuL5(H2O)] [CuL6], [CuL7], [CuL8](OAc) and [CuL9], where L1L9 represents Schiff base ligands [derived by the condensation of 5‐hydroxyflavone with 4‐aminoantipyrine (L1), o‐aminophenol (L2), o‐aminobenzoic acid (L3), o‐aminothiazole (L4), thiosemicarbazide (L5), 4‐aminoantipyrine‐o‐aminophenol (L6), 4‐aminoantipyrine‐o‐aminobenzoic acid (L7), 4‐aminoantipyrine‐o‐aminothiazole(L8) and 4‐aminoantipyrine‐thiosemicarbazide (L9)]. The spectral and magnetic results of the Cu(II) complexes exhibit square planar geometry. The DNA binding properties of copper complexes were studied by using electronic absorption spectra, viscosity and thermal denaturation experiments. The results show that the complexes were interacting with calf thymus (CT DNA). The in vitro antimicrobial activities of the investigated compounds were tested against the bacterial species and fungal species. Superoxide dismutase and antioxidant activities of the copper complexes have also been studied. Copyright © 2011 John Wiley & Sons, Ltd.

Relationships between Structure and Anti-oxidative Effects of Hydroxyflavones

All of these molecules are flavones, which are subclasses of flavonoids with a common feature of a C6-C3-C6 skeleton. Flavonoids can be classified on the basis of the substitution patterns of the C ring, such as flavanone, flavonol, isoflavone, and flavone. Among these, flavone, flavanone, and flavonol are determined by the C3 ring in the C6-C3-C6 skeleton, which is named the C ring. Flavones contain both a ketone group at the C-4 position and a double bond between C-2 and C-3 of the C ring. Note that primuletin, chrysin, and luteolin have only minor differences in their hydroxyl groups, but show considerable differences in their biological activities. To elucidate the relation-ships between the structures of flavones and their biological activities based on the numbers and/or positions of hydroxyl groups, we examined the anti-oxidative effects of 20 hydroxy-flavone derivatives. The 1,1-diphenyl-2-picryl-hydrazyl (DPPH) assay was used to screen for anti-oxidative effects in our study.Twenty hydroxyflavones consisting of five monohydroxy-flavones, nine dihydroxyflavones, four trihydroxyflavones,

1H and 13C‐NMR data of hydroxyflavone derivatives

Many hydroxyflavone derivatives have been found in nature and shown to have many biological functions. Because their function is changed by the position and number of hydroxyl group, their structural identification is a fundamental and necessary step for understanding their functions. In the present study, the complete 1H and 13C NMR spectral assignments were presented for 6 hydroxyflavones, and NMR data of additional 14 hydroxyflavone derivatives were compared with those of the 6 hydroxyflavones. In addition, the partially incorrect NMR data of two of the dihydroxyflavones whose NMR data were previously reported were corrected.

Proton and charge transfer reactions dynamics of a hydroxyflavone derivative in a polar solvent and in a cyclodextrin nanocavity

In this work, we report on the observation of ultrafast intramolecular charge- and proton-transfer reactions of 4′-dimethylaminoflavonol (DMAF) in N, N-dimethyl formamide and in γ-cyclodextrin (γ-CD) solution. Upon femtosecond excitation an intramolecular charge transfer (ICT) reaction takes place to produce an ICT structure in ∼200 fs. This structure may undergo a proton transfer reaction to generate a zwitterionic (Z) form in 2–3 ps, or relaxes in its potential energy well, to later equilibrate with that of Z in hundreds of ps. Addition of γ-CD does not significantly affect the fast dynamics of the formed anion. The fs-emission signals of the parent molecule, 3-hydroxyflavone, indicate that the dimethyl amino group in DMAF enhances the rate constant of intermolecular proton-transfer and intramolecular charge-transfer reactions.

Complexation effect of γ-cyclodextrin on a hydroxyflavone derivative: Formation of excluded and included anions

In this work, we report on steady-state and time-resolved picosecond measurements of the effect of γ-cyclodextrin (CD) on the UV–visible absorption and fluorescence characteristics of 4′- dimethylaminoflavonol (DMAF) in N, N-dimethyl formamide (DMF). We first show that the electronically excited DMAF in DMF undergoes an equilibrated reaction between an intramolecular charge transfer (ICT) and a tautomer (T) formed after an intramolecular proton transfer in the former. A very small amount of anion of DMAF is also found at the ground state. Upon addition of CD, the results show larger formation of anions of DMAF through H-bonding interactions inside of the CD and at its gate giving birth to inclusion and capped complexes, respectively. Both anions emit at the same regions. However, the encapsulated one has a shorter fluorescence lifetime (∼1 ns) due to the lower polarity of the caging nano-cavity when compared to DMF. Rotational times of free (97 ps) and complexed (130 and 770 ps) DMAF agree with those expected from the hydrodynamics theory and the optimized structures using PM3 calculations. The results add new information on the interaction of CD with phenol-containing probes, and it may be relevant to the design of sensors using these nano-hosts and to drug delivery field using CD.

Inhibition of Efflux Transporter-Mediated Fungicide Resistance in Pyrenophora tritici-repentis by a Derivative of 4′-Hydroxyflavone and Enhancement of Fungicide Activity

Populations of the causal agent of wheat tan spot, Pyrenophora tritici-repentis, that are collected from fields frequently treated with reduced fungicide concentrations have reduced sensitivity to strobilurin fungicides and azole fungicides (C14-demethylase inhibitors). Energy-dependent efflux transporter activity can be induced under field conditions and after in vitro application of sublethal amounts of fungicides. Efflux transporters can mediate cross-resistance to a number of fungicides that belong to different chemical classes and have different modes of action. Resistant isolates can grow on substrata amended with fungicides and can infect plants treated with fungicides at levels above recommended field concentrations. We identified the hydroxyflavone derivative 2-(4-ethoxy-phenyl)-chromen-4-one as a potent inhibitor of energy-dependent fungicide efflux transporters in P. tritici-repentis. Application of this compound in combination with fungicides shifted fungicide-resistant P. tritici-repentis isolates back to normal sensitivity levels and prevented infection of wheat leaves. These results highlight the role of energy-dependent efflux transporters in fungicide resistance and could enable a novel disease management strategy based on the inhibition of fungicide efflux to be developed.

Femtosecond observation of intramolecular charge- and proton-transfer reactions in a hydroxyflavone derivative

In this Letter, we report on direct observation of ultrafast intramolecular charge-transfer (ICT) reaction versus proton motion in 4′-dimethylaminoflavonol (DAMF) in solution. In an apolar medium, upon femtosecond excitation of a non planar structure of DMAF the ICT does not occur, and an abnormally slow (2 ps) proton motion takes place. In polar solvents, the ICT is very fast (100–200 fs) and the formed structure is stabilised in an extent that proton motion takes place in few or tens of ps. To our best knowledge, this is the first observation of competitive and related charge and proton transfers dynamics.

Tuning the mechanism of proton-transfer in a hydroxyflavone derivative

In this Letter, we report on steady-state and time-resolved emission studies of 4 ′-dimethylaminoflavonol (DAMF) in two families of solvents where we observed a reversible or an irreversible proton motion in the ultrafast formed charge-transfer (CT) state of DMAF. The slower (picosecond) proton-transfer time constant of DMAF compared to the femtosecond one observed in non-substituted 3-hydroxyflavones is due the involvement of an intramolecular CT. For the reversible situation, increasing the polarity of the medium increases the rate of proton motion.

The crystal structures and hydrogen-bond properties of three 3-hydroxy-flavone derivatives

The room temperature crystal structures of three hydroxy-flavone derivatives have been solved. These compounds are important as molecular prototypes for picosecond laser studies of ultrafast excited-state proton transfer mechanism. They all have a cyclic intramolecular hydrogen-bond between the carbonyl group and the 3-hydroxy group, but their intermolecular hydrogen-bond patterns are distinctly different. In 3-hydroxy-flavone, I, an intermolecular hydrogen bond was found which links neighboring molecules into a polymer chain along a two-fold screw axis; in 2′-methyl-3-hydroxy-flavone, II, there are no intermolecular H-bonds; in 3′-methyl-3-hydroxyflavone, III, a centric hydrogen-bonded dimer is formed. The relationships between molecular conformation and solid-state aggregate patterns of 3-hydroxyflavones and related molecules are discussed in terms of possible ground state solute—solvent and solvent—solute solution structures. Crystal data: I, a = 11.427(3), b = 18.255(4) c = 5.457(2) Å; S.G. = P2 12 12 1; Z = 4; 803 observed reflections, Mo Kα, R = 0.036, R W = ,0.057;II, a = 21.928(8), b = 16.914(5), c = 6.785(5) Å; S.G. = Pbca, Z = 8, 1929 observed reflections, Cu Kα, R = 0.043, R W = 0.057; III, a = 13.868(4), b = 17.494(3), c = 5.133(2) Å, β = 95.40(2); S.G. = P2 1/ n; Z =4.2122 observed reflections; R = 0.054, R W = 0.054.