Dihydroxy Groups Research Articles

Quercetin as a tyrosinase inhibitor: Inhibitory activity, conformational change and mechanism

Quercetin, a flavonoid compound, was found to inhibit both monophenolase and diphenolase activities of tyrosinase, and its inhibition against diphenolase activity was in a reversible and competitive manner with an IC50 value of (3.08±0.74)×10−5molL−1. Quercetin bound to tyrosinase driven by hydrophobic interaction, thereby resulted in a conformational change of tyrosinase and its intrinsic fluorescence quenching. Tyrosinase had one binding site for quercetin with the binding constant in the order of magnitude of 104Lmol−1. The molecular docking revealed that quercetin bound to the active site of tyrosinase and chelated a copper with the 3′, 4′-dihydroxy groups. It can be deduced that the chelation may prevent the entrance of substrate and then inhibit the catalytic activity of tyrosinase. These findings may be helpful to understand the inhibition mechanism of quercetin on tyrosinase and functional research of quercetin in the treatment of pigmentation disorders.

Comprehensive study on excited state intramolecular proton transfer in 2-(benzo[d]thiazol-2-yl)-3-methoxynaphthalen-1-ol and 2-(benzo[d]thiazol-2-yl)naphthalene-1,3-diol: Effect of solvent, aggregation, viscosity and TDDFT study

Abstract Three compounds DMT, MMT and DHT having dimehtoxy, mono-hydroxy and di-hydroxy groups respectively were prepared. Environmental interactions dependent photophysical properties especially excited state intramolecular proton transfer (ESIPT), solvatochromism, aggregation induced emission enhancement (AIEE) and viscosity dependent emission characteristics were studied. The effect of solvent polarity on ESIPT dynamics were studied using UV–vis and emission spectroscopy along with aggregation induced enhanced emission and viscosity effect. MMT and DHT showed unexpected and contrasting behavior in the solvents which are in good agreement with the density functional theory and time dependent density functional theory findings. Aggregation and viscosity study showed that cis-keto emission increased drastically in the aggregate state and highly viscous state due to restricted intramolecular rotation increasing the population of required cis enol rotamer (E). The study directs the potential applications of such molecules for advanced optoelectronics and viscosity based investigations.

STUDY OF CONFORMATIONAL PREFERENCES OF ERYTHRO-CAROLIGNAN E ASSESSED BY THE COUPLING BETWEEN H7'-H8' IN DIFFERENT NMR SOLVENTS

<p><em>Erythro</em>-carolignan E (<strong>1</strong>) has been obtained from the ethanol extract of the wood bark of <em>Durio affinis</em> Becc. This research was conducted in order to prove that conformational preferences of compound <strong>1</strong> were solvent dependent. On the basis of <sup>1</sup>H-NMR data, the relative configuration of compound <strong>1</strong> was characterized by a coupling constant (<sup>3</sup><em>J</em><sub>HH</sub>) value of 3.3 Hz at H-7' in CDCl<sub>3</sub>. The coupling constant (<sup>3</sup><em>J</em><sub>HH</sub>) values of H-7' in compound <strong>1</strong> has changed to 4.1 Hz and 5.3 Hz in pyridine-<em>d</em><sub>5</sub> and acetonitrile-<em>d</em><sub>3</sub> respectively. As a result, the conformation of compound <strong>1</strong> at C7'-C8' has changed in different NMR solvents. In conclusion, structure of<em>erythro</em>-carolignan E that contains a dihydroxy group at C7'-C8' is able to change in different NMR solvent.</p>

Homochiral 2D Porous Covalent Organic Frameworks for Heterogeneous Asymmetric Catalysis.

There have been breakthroughs in the development of covalent organic frameworks (COFs) with tunability of composition, structure, and function, but the synthesis of chiral COFs remains a great challenge. Here we report the construction of two-dimensional COFs with chiral functionalities embedded into the frameworks by imine condensations of enantiopure TADDOL-derived tetraaldehydes with 4,4'-diaminodiphenylmethane. Powder X-ray diffraction and computer modeling together with pore size distribution analysis show that one COF has a twofold-interpenetrated grid-type network and the other has a non-interpenetrated grid network. After postsynthetic modification of the chiral dihydroxy groups of TADDOL units with Ti(O(i)Pr)4, the materials are efficient and recyclable heterogeneous catalysts for asymmetric addition of diethylzinc to aldehydes with high enantioselectivity. The results reported here will greatly expand the scope of materials design and engineering for the creation of new types of functional porous materials.

Synthesis of (2S,3R,4R)-3,4-dihydroxyarginine and its inhibitory activity against nitric oxide synthase

A synthesis of (2S,3R,4R)-3,4-dihydroxyarginine, a metabolic intermediate of streptothricin, was accomplished. The (3R,4R)-dihydroxy groups were constructed by asymmetric syn-dihydroxylation of (E)-alkene, which was obtained by cross-metathesis of allylamine and l-vinylglycine derivatives. The synthesis of (2S,3S,4S)-3,4-dihydroxyarginine was also achieved in the same manner. The (2S,3R,4R)-3,4-dihydroxyarginine exhibited inhibitory activity against inducible nitric oxide synthase, unlike (2S,3S,4S)-3,4-dihydroxyarginine.

Enhanced characterization of oil sands acid-extractable organics fractions using electrospray ionization-high-resolution mass spectrometry and synchronous fluorescence spectroscopy.

The open pit oil sands mining operations north of Fort McMurray, Alberta, Canada, are accumulating tailings waste at a rate approximately equal to 4.9 million m(3) /d. Naphthenic acids are among the most toxic components within tailings to aquatic life, but structural components have largely remained unidentified. In the present study, electrospray ionization high-resolution mass spectrometry (ESI-HRMS) and synchronous fluorescence spectroscopy (SFS) were used to characterize fractions derived from the distillation of an acid-extractable organics (AEO) mixture isolated from oil sands process-affected water (OSPW). Mean molecular weights of each fraction, and their relative proportions to the whole AEO extract, were as follows: fraction 1: 237 Da, 8.3%; fraction 2: 240 Da, 23.8%; fraction 3: 257 Da, 26.7%; fraction 4: 308 Da, 18.9%; fraction 5: 355 Da, 10.0%. With increasing mean molecular weight of the AEO fractions, a concurrent increase occurred in the relative abundance of nitrogen-, sulfur-, and oxygen-containing ions, double-bond equivalents, and degree of aromaticity. Structures present in the higher-molecular-weight fractions (fraction 4 and fraction 5) suggested the presence of heteroatoms, dicarboxyl and dihydroxy groups, and organic acid compounds with the potential to function as estrogens. Because organic acid compositions become dominated by more recalcitrant, higher-molecular-weight acids during natural degradation, these findings are important in the context of oil sands tailings pond water remediation.

Synthetic studies on actinorhodin and γ-actinorhodin: synthesis of deoxyactinorhodin and deoxy-γ-actinorhodin/crisamicin A isomer.

A strategy based on bidirectional Dötz benzannulation and the oxa-Pictet-Spengler reaction toward the synthesis of actinorhodin and γ-actinorhodin has been explored. This work has resulted in the synthesis of deoxyactinorhodin and deoxy-γ-actinorhodin. The latter is a regioisomer of crisamicin A (which has 10,10'-dihydroxy groups).

Chromones and their derivatives as radical scavengers: a remedy for cell impairment.

Chromones (1-benzopyran-4-ones) are natural occurring compounds present in representative amounts in a normal human diet and are associated with interesting physiological activities such as antiinflammatory, antidiabetic, antitumor, anticancer etc. These biological activities are thought to be related to the antioxidant properties of chromones i.e. to neutralize active oxygen and to cut off free radicals processes that can delay or inhibit cell impairment which leads to various diseases. In this review, we have summarized the literature reports published in about 70 research articles during the period January 2004 to March 2014 on more than 400 naturally as well as the synthetically derived chromone derivatives having antioxidant potential. The literature reports suggest that the double bond, a carbonyl group of chromone and 3´,4´-dihydroxy group (catechol) in ring B along with the C-3 and C-5 hydroxyl groups are important for radical scavenging activity. In turn, a decrease in the radical scavenging potential has been observed upon methylation / glycosylation of the hydroxyl groups on chromone nucleus.

Engineering chiral porous metal-organic frameworks for enantioselective adsorption and separation.

The separation of racemic molecules is of substantial significance not only for basic science but also for technical applications, such as fine chemicals and drug development. Here we report two isostructural chiral metal-organic frameworks decorated with chiral dihydroxy or -methoxy auxiliares from enantiopure tetracarboxylate-bridging ligands of 1,1'-biphenol and a manganese carboxylate chain. The framework bearing dihydroxy groups functions as a solid-state host capable of adsorbing and separating mixtures of a range of chiral aromatic and aliphatic amines, with high enantioselectivity. The host material can be readily recycled and reused without any apparent loss of performance. The utility of the present adsorption separation is demonstrated in the large-scale resolution of racemic 1-phenylethylamine. Control experiments and molecular simulations suggest that the chiral recognition and separation are attributed to the different orientations and specific binding energies of the enantiomers in the microenvironment of the framework.

Turn-on Type Chemical Sensing of Vitamin K4 by Fluorene Dendrimers with Naphthalene Segments

G1 and G2 fluorene dendrimers with naphthalene termini were synthesized as a fluorescence turn-on type chemical sensor for vitamin K4. The fluorene dendrimers were prepared by Williamson ether reaction between the fluorene core with dihydroxy groups and dendritic naphthalene segments with methylene chloride by a convergent method. We investigated the relationship between the dendrimer generation and vitamin K4 recognition of fluorene dendrimer with naphthalene termini in CHCl3. Addition of vitamin K4 enhanced the fluorescence intensity of the fluorene dendrimer. Especially, the G2 fluorene dendrimer was found to be an effective chemical sensor for vitamin K4 and better than the G1 fluorene dendrimer.

Chiral Porous TADDOL-Embedded Organic Polymers for Asymmetric Diethylzinc Addition to Aldehydes

Abstract Two chiral porous organic polymers (CPOPs) were synthesized by linking a TADDOL-embedded building block with arylethynylenes units. The CPOPs are highly stable to thermal treatment, moisture, acidity, and basicity. The dihydroxy groups of TADDOL inside the pores promise the CPOPs as good asymmetric catalysts after postsynthesis modification with a secondary metal center. After being treated with Ti(OiPr)4, the CPOPs could be used as highly effective and reusable heterogeneous catalyst for asymmetric diethylzinc addition to aldehydes with up to 99% conversion and 95% ee. This work promises the potential of generating chiral solid catalysts with unique and practically useful enantioselective functions via a modular approach.

利用"Click"反应制备含有(R)-(+)-BINOL的有机聚合物及其钛配合物在不对称加成反应中的催化性能

An organic polymer containing chiral(R)-(+)-1,1′-binaphthol[(R)-(+)-BINOL] building blocks(Polymer) has been prepared through Click reaction(Huisgen 1,3-dipolar cycloaddition) of(R)-(+)-6,6′-diethynyl-1,1′-binaphthol and 1,4-diazidobenzen in the presence of Copper(Ⅰ).The composition,structure and morphology of Polymer were characterized by Fourier transform infrared(FTIR) spectrometer,powder X-ray diffractometer(XRD) and scanning electron microscope(SEM).The Polymer was coordinated to titanium of Ti(OiPr)4 through chiral dihydroxy groups in(R)-(+)-BINOL to synthesize a new heterogeneous chiral metal catalyst(Polymer-Ti),which exhibited extremely high conversion and good enantioselectivity in asymmetric addition reaction of diethylzinc to multiple aromatic aldehydes.Also,Polymer-Ti catalyst displayed stable catalytic activities in multi-recycle of asymmetric addition reaction of diethylzinc to benzaldehyde.

A single amino acid determines position specificity of an Arabidopsis thaliana CCoAOMT-like O-methyltransferase

Caffeoyl-coenzyme A O-methyltransferase (CCoAOMT)-like proteins from plants display a conserved position specificity towards the meta-position of aromatic vicinal dihydroxy groups, consistent with the methylation pattern observed in vivo. A CCoAOMT-like enzyme identified from Arabidopsis thaliana encoded by the gene At4g26220 shows a strong preference for methylating the para position of flavanones and dihydroflavonols, whereas flavones and flavonols are methylated in the meta-position. Sequence alignments and homology modelling identified several unique amino acids compared to motifs of other CCoAOMT-like enzymes. Mutation of a single glycine, G46 towards a tyrosine was sufficient for a reversal of the unusual para- back to meta-O-methylation of flavanones and dihydroflavonols.

Investigation of reaction between quercetin and Au(iii) in acidic media: mechanism and identification of reaction products

The aim of the present paper was to investigate the reaction of quercetin, the flavonol very often used as a dietary supplement, with [AuCl4]− ions. The reaction was studied spectrophotometrically using the equimolar solutions in 1 : 1 water–methanol at pH ∼ 2. The spectrophotometric data indicated the formation of the products with an absorption maximum at 295 nm in all cases, characteristic of the oxidized forms of quercetin. HPLC coupled with DAD and LC-MS analysis of the reaction products suggested that the oxidation of quercetin resulted in the generation of similar metabolites including quinone and various oxidized quercetin–solvent adducts. In addition, cyclic voltammetric measurements confirmed that under applied experimental conditions, the reduction of Au(III) to Au(0) took place. The reduction species in the reaction mixture were Au(III) ions, while Au(I) disproportionates back to Au(III) and Au(0). The newly generated Au(III) ions further oxidized 3′,4′-dihydroxy groups of quercetin adducts obtained after first 2e− oxidation, giving the final reaction products. Based on the identification of reaction products, the reaction mechanism for the oxidation of quercetin in the presence of Au(III) which involves two 2e− transfer processes was proposed.

The role of CCoAOMT1 and COMT1 in Arabidopsis anthers

Arabidopsis caffeoyl coenzyme A dependent O-methyltransferase 1 (CCoAOMT1) and caffeic acid O-methyltransferase 1 (COMT1) display a similar substrate profile although with distinct substrate preferences and are considered the key methyltransferases (OMTs) in the biosynthesis of lignin monomers, coniferyl and sinapoylalcohol. Whereas CCoAOMT1 displays a strong preference for caffeoyl coenzyme A, COMT1 preferentially methylates 5-hydroxyferuloyl CoA derivatives and also performs methylation of flavonols with vicinal aromatic dihydroxy groups, such as quercetin. Based on different knockout lines, phenolic profiling, and immunohistochemistry, we present evidence that both enzymes fulfil distinct, yet different tasks in Arabidopsis anthers. CCoAOMT1 besides its role in vascular tissues can be localized to the tapetum of young stamens, contributing to the biosynthesis of spermidine phenylpropanoid conjugates. COMT1, although present in the same organ, is not localized in the tapetum, but in two directly adjacent cells layers, the endothecium and the epidermal layer of stamens. In vivo localization and phenolic profiling of comt1 plants provide evidence that COMT1 neither contributes to the accumulation of spermidine phenylpropanoid conjugates nor to the flavonol glycoside pattern of pollen grains.

Tyrosinase inhibitory constituents from the bark of Peltophorum dasyrachis (yellow batai)

Tyrosinase inhibitory activity-guided fractionation of the bark of Peltophorum dasyrachis (yellow batai) led to the isolation of the six active compounds which were characterised as six flavonoids: apigenin (1), (+)-2,3-trans-dihydrokaempferol (2), (+)-2,3-trans-dihydrokaempferol-3-O-α-L-rhamnoside (3), (+)-4′,7-dimethoxy-2,3-trans-dihydroquercetin (4), (+)-2,3-trans-dihydroquercetin (5) and (–)-2,3-trans-dihydroquercetin-3-O-α-L-rhamnoside (6). All compounds were isolated for the first time from the bark of P. dasyrachis. Moreover, all compounds were evaluated for tyrosinase activities towards L-DOPA as the substrate. We observed that compounds 2 and 5 showed potent inhibitory effects (IC50 values were 126 ± 3.2 and 210 ± 5.8 µM, respectively). In general, for flavonoids the 3′,4′-dihydroxy group's substituent is a more potent inhibitor than the 4′-hydroxy group substituent, i.e. quercetin > kaempferol. Interestingly, our result in the oxidation of L-DOPA showed that the 4′-hydroxy group substituent (compound 2) is a more potent inhibitor than the 3′,4′-dihydroxy group substituent (compound 5). This result showed a new relationship between tyrosinase inhibitory activities and flavonoids. The kinetic analyses by Lineweaver–Burk plots showed that both the compounds 2 and 5 behaved as competitive inhibitors of L-DOPA oxidation.

Isolation and Tyrosinase Inhibitory Effects of Polyphenols from the Leaves of Persimmon, Diospyros kaki

The main polyphenols were isolated from the leaves of six selected persimmon cultivars. Seven compounds were obtained by reverse-phase HPLC, and their structures were elucidated by multiple NMR measurements. These compounds are hyperoside, isoquercitrin, trifolin, astragalin, chrysontemin, quercetin-3-O-(2''-O-galloyl-β-D-glucopyranoside) (QOG), and kaempferol-3-O-(2''-O-galloyl-β-D-glucopyranoside) (KOG). Their inhibitory activity was tested against tyrosinase for the oxidation of L-DOPA, and only chrysontemin showed inhibitory activity. To investigate the differences of their inhibitory effects, the tyrosinase inhibitory activities of their aglycons, cyanidin, quercetin, and kaempferol, were also tested. As a result, it was confirmed that the most influential moiety for tyrosinase inhibition was the 3',4'-dihydroxy groups of the catechol moiety. Moreover, the tyrosinase inhibitory activity of chrysontemin, which was identified in persimmon leaves for the first time, is supported by a simulated model of chrysontemin docking into mushroom tyrosinase.

Finding more active antioxidants and cancer chemoprevention agents by elongating the conjugated links of resveratrol

Resveratrol is the subject of intense research as a natural antioxidant and cancer chemopreventive agent. There has been a great deal of interest and excitement in understanding its action mechanism and developing analogs with antioxidant and cancer chemoprevention activities superior to that of the parent compound in the past decade. This work delineates that elongation of the conjugated links is an important strategy to improve the antioxidant activity of resveratrol analogs, including hydrogen atom- or electron-donating ability in homogeneous solutions and antihemolysis activity in heterogeneous media. More importantly, C3, a triene bearing 4,4′-dihydroxy groups, surfaced as an important lead compound displaying remarkably increased antioxidant, cytotoxic, and apoptosis-inducing activities compared with resveratrol.

Structural, Electronic, and Optical Properties of Representative Cu−Flavonoid Complexes

We present density functional theory (DFT) results on the structural, electronic, and optical properties of Cu-flavonoid complexes for molar ratios 1:1, 1:2, and 1:3. We find that the preferred chelating site is close to the 4-oxo group and in particular the 3-4 site followed by the 3'-4' dihydroxy group in ring B. For the Cu-quercetin complexes, the large bathochromic shift of the first absorbance band upon complexation, which is in good agreement with experimental UV-vis spectra, results from the reduction of the electronic energy gap. The HOMO states for these complexes are characterized by pi-bonding between the Cu d orbitals and the C, O p orbitals except for the case of 1:1 complex (spin minority), which corresponds to sigma-type bonds. The LUMO states are attributed to the contribution of Cu p(z) orbitals. Consequently, the main features of the first optical absorption maxima are essentially due to pi --> pi transitions, while the 1:1 complex exhibits also sigma --> pi transitions. Our optical absorption calculations based on time-dependent DFT demonstrate that the 1:1 complex is responsible for the spectroscopic features at pH 5.5, whereas the 1:2 complex is mainly the one responsible for the characteristic spectra at pH 7.4. These theoretical predictions explain in detail the behavior of the optical absorption for the Cu-flavonoid complexes observed in experiments and are thus useful in elucidating the complexation mechanism and antioxidant activity of flavonoids.

Characteristic of neuraminidase inhibitory xanthones from Cudrania tricuspidata

Natural polyphenolic compounds generally transpire to show relatively low inhibition against glycosidase including neuraminidase. In addition the inhibition modes of such compounds are rarely competitive. In this manuscript, a series of xanthone derivatives from Cudrania tricuspidata are shown to display nanomolar inhibitor activity against neuraminidase (EC 3.2.1.18) as well as competitive inhibition modes. Compound 8 bearing vicinal dihydroxy group on the A-ring displays nanomolar activity (IC 50 = 0.08 ± 0.01 μM), a 200-fold increase in activity relative to that of the first reported xanthone-derived neuraminidase inhibitor, mangiferin (IC 50 = 16.2 ± 4.2 μM). The 6,7-vicinal dihydroxy group plays a crucial role for inhibitory activity because compound 4, which has one of these hydroxyl groups prenylated was inactive (33% at 200 μM), whereas other compounds ( 1– 3 and 6– 8) showed nanomolar activity (0.08–0.27 μM) and competitive inhibition modes. Interestingly all inhibitors manifested enzyme isomerization inhibition against neuraminidase. The most potent inhibitor, compound 8 showed similar interaction with a transition-state analogue of neuraminic acid in active site.