102-32-9Relevant academic research and scientific papers
Hydroxylation of p-substituted phenols by tyrosinase: Further insight into the mechanism of tyrosinase activity
Munoz-Munoz, Jose Luis,Berna, Jose,Garcia-Molina, Maria del Mar,Garcia-Molina, Francisco,Garcia-Ruiz, Pedro Antonio,Varon, Ramon,Rodriguez-Lopez, Jose N.,Garcia-Canovas, Francisco
, p. 228 - 233 (2012)
A study of the monophenolase activity of tyrosinase by measuring the steady state rate with a group of p-substituted monophenols provides the following kinetic information: kcatm and the Michaelis constant, KMm. Analysis of these data taking into account chemical shifts of the carbon atom supporting the hydroxyl group (δ) and σp+, enables a mechanism to be proposed for the transformation of monophenols into o-diphenols, in which the first step is a nucleophilic attack on the copper atom on the form Eox (attack of the oxygen of the hydroxyl group of C-1 on the copper atom) followed by an electrophilic attack (attack of the hydroperoxide group on the ortho position with respect to the hydroxyl group of the benzene ring, electrophilic aromatic substitution with a reaction constant ρ of -1.75). These steps show the same dependency on the electronic effect of the substituent groups in C-4. Furthermore, a study of a solvent deuterium isotope effect on the oxidation of monophenols by tyrosinase points to an appreciable isotopic effect. In a proton inventory study with a series of p-substituted phenols, the representation of kcatfn/kcatf0 against n (atom fractions of deuterium), where kcatfn is the catalytic constant for a molar fraction of deuterium (n) and kcatf0 is the corresponding kinetic parameter in a water solution, was linear for all substrates. These results indicate that only one of the proton transfer processes from the hydroxyl groups involved the catalytic cycle is responsible for the isotope effects. We suggest that this step is the proton transfer from the hydroxyl group of C-1 to the peroxide of the oxytyrosinase form (Eox). After the nucleophilic attack, the incorporation of the oxygen in the benzene ring occurs by means of an electrophilic aromatic substitution mechanism in which there is no isotopic effect.
Nitration and hydroxylation of substituted phenols by peroxynitrite. Kinetic feature and an alternative mechanistic view
Nonoyama, Nobuaki,Chiba, Kazuhiko,Hisatome, Kaori,Suzuki, Hitomi,Shintani, Futoshi
, p. 6933 - 6937 (1999)
The reaction of peroxynitrite (ONOO-) with a series of para-substituted phenols has been examined in aqueous phosphate buffer and acetonitrile solutions. Major products were the corresponding 2-nitro derivative and the 4-substituted catechol. Kinetic study showed good correlation with Hammett σ(p)+ parameters and reduction potentials, suggesting the possible one-electron transfer process involving the nitrosoniun ion (NO+) as initial electrophile generated from peroxynitrous acid.
A kinetic investigation of the pulmonary metabolism of dopamine in rats shows marked differences compared with noradrenaline
Scarcella,Bryan-Lluka
, p. 491 - 499 (1995)
The aim of this study was to investigate the deamination of dopamine in the intact pulmonary circulation of isolated lungs of the rat. The first part of the study showed that dopamine is not converted to noradrenaline by dopamine-β-hydroxylase (DBH) when dopamine is perfused through isolated lung preparations with monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT) inhibited. Hence, it was not necessary to inhibit DBH in subsequent experiments. The metabolite profile for deamination of dopamine in the lungs was examined by determining whether MAO and semicarbazide-sensitive amine oxidases (SSAO) contribute to the deamination of dopamine (and noradrenaline), and by determining the activity of MAO (k(MAO)) for the metabolism of dopamine. Lungs were perfused with 1 nmol/l 3H-dopamine or 3H-noradrenaline with COMT inhibited and, in experiments to determine the contribution of SSAO to deamination, with MAO inhibited. Inhibition of MAO reduced the deamination of dopamine and noradrenaline by 99.8% and 98.6%, respectively, indicating that MAO, and not SSAO, was responsible for deamination of the catecholamines in the lungs. The k(MAO) value for deamination of dopamine was 3.89 min-1. Further experiments were carried out to determine the contributions of MAO-A and MAO-B to the deamination of dopamine in lungs perfused with 1 nmol/l3H-dopamine and 100 nmol/l lazabemide or 300 nmol/l Ro41-1049, respectively. The values of k(MAO-A) and k(MAO-B) were 3.05 min-1 and 0.626 min-1, respectively.
Layer-by-Layer coated tyrosinase: An efficient and selective synthesis of catechols
Guazzaroni, Melissa,Crestini, Claudia,Saladino, Raffaele
, p. 157 - 166 (2012)
Agaricus bisporous tyrosinase was immobilized on commercial available epoxy-resin EupergitC250L and then coated by the Layer-by-Layer method (LbL). The two novel heterogeneous biocatalysts were characterized for their morphology, pH and storage stability, kinetic properties (Km, V max, Vmax/Km) and reusability. These biocatalysts were used for the efficient and selective synthesis of bioactive catechols under mild and environmental friendly experimental conditions. Ascorbic acid was added in the reaction medium to inhibit the formation of ortho-quinones, thus avoiding the known enzyme suicide inactivation process. Catechols were obtained mostly in quantitative yields and conversion of substrate. Tyrosinase immobilized on EupergitC250L and coated by the LbL method showed better catalytic activities, higher pH and storage stability, and reusability with respect to immobilized uncoated tyrosinase. Since chemical procedures to synthesize catechols are often expensive and with high environmental impact, the use of immobilized tyrosinase represents an efficient alternative for the preparation of this family of bioactive compounds.
A Heterogeneous Recyclable Rhodium-based Catalyst for the Reduction of Pyridine Dinucleotides and Flavins
Deng, Yifan,Odziomek, Mateusz,Sanchez, Clement,Back, Olivier,Mougel, Victor,Fontecave, Marc
, p. 1236 - 1243 (2020)
Reduced pyridine nucleotides and flavins are important enzyme cofactors that require continuous regeneration for biotechnological development of the corresponding enzymes. This can be achieved with the assistance of a dehydrogenase system or by reduction with formate catalysed by a soluble organometallic {[Cp*Rh(bpy)(H2O)]2+} (Cp=pentamethylcyclopentadienyl; bpy=bipyridine) complex. Here, we report that this Rh complex, once immobilized on bypiridine-periodic mesoporous organosilica, displays catalytic activity for flavin (including FAD, FMN and riboflavin) and NAD(P)+ reduction by formate. The recyclability of this solid catalyst makes it possible to achieve up to 20 cycles of FAD reduction without activity loss. This recyclable heterogeneous catalyst can also be used to assist a complex NADH-, FAD- and O2-dependent monooxygenase system, allowing several cycles of transformation of a phenol into the corresponding catechol.
The effects of 1-methyl-4-phenylpyridinium ion (MPP+) on the efflux and metabolism of endogenous dopamine in rat striatal slices
Snape,Pileblad,Ekman,Magnusson,Carlsson,Engel
, p. 620 - 626 (1988)
1-Methyl-4-phenylpyridinium ion (MPP+) was shown to accumulate concentration-dependently in slices from rat striatum. At 10 μM MPP+, the tissue concentration was found to be 118 ± 9 μM following 75 min of incubation. The accumulation of MPP+ was reduced in the presence of 10 μM of the selective dopamine uptake inhibitor GBR 12909 (-50%) or by destruction of the dopaminergic terminals by complete hemisection of the forebrain 4 days before the experiments (-75%). Accumulation of MPP+ in the catecholamine-poor occipital cortex and cerebellum was only 25% of that obtained in striatum. Reserpine pretreatment of the rats in-vivo did not modify the accumulation of MPP+ in the striatal slices. MPP+ (1-10 μM) increased the net efflux of dopamine and reduced the efflux of the dopamine metabolite DOPAC from the striatal slices. The effect on dopamine was readily diminished if MPP+, after a 15 min incubation, was then omitted from the medium. In contrast, the DOPAC efflux was reduced for 75 min even though MPP+ was present in the incubation medium only for the first 15 min. In the presence of the monoamine oxidase inhibitor, pargyline (350 μM), MPP+ also produced an increase in dopamine efflux. In normal medium, the presence of the dopamine uptake inhibitor GBR 12909 (10 μM), or the absence of calcium, failed to modify the MPP+-induced increase in dopamine efflux. MPP+ also increased dopamine efflux from slices from reserpinized rats. In normal medium, MPP+ (10 μM) was much more effective than GBR 12909 (10 μM) in increasing dopamine efflux, whereas in the presence of pargyline both drugs were equally effective. It is suggested that, in rat striatal slices, MPP+ is selectively accumulated within the dopaminergic nerve terminals by means of a carrier mediated transport, sensitive to GBR 12909. It is concluded that MPP+ increases dopamine efflux largely by inhibiting monoamine oxidase and by inhibiting dopamine uptake. These data are discussed in relation to the previously observed action of MPTP on dopamine metabolism in mouse brain in-vivo.
Bioavailability and pharmacokinetics of an oral dopamine prodrug in dogs.
Murata,Noda,Kohno,Samejima
, p. 812 - 814 (1989)
The bioavailability and pharmacokinetics of an oral dopamine prodrug, N-(N-acetyl-L-methionyl)O,O-bis(ethoxycarbonyl)dopamine (1), were examined in dogs, and the mechanism of its absorption and bioactivation was discussed. Compound 1 showed a plasma dopamine concentration that was several times higher than that of dopamine (DA) following oral administration to dogs, while the plasma concentrations of dopamine-30-sulfate (DA-SO4) and 3,4-dihydroxyphenylacetic acid (DOPAC) are lower in comparison with that of DA. The conversion of 1 to DA occurred in proportion to the dose administered. Compound 1 also showed a plasma DA concentration that was several times higher than that of other DA prodrugs reported hitherto. In dog plasma, in vitro, 1 was converted to its deethoxycarbonylated form, N-(N-acetyl-L-methionyl)dopamine (2), while other related compounds, N-(L-methionyl)dopamine (3), N-(L-methionyl)O,O-bis(ethoxycarbonyl)-dopamine (4), and O,O-bis(ethoxycarbonyl)dopamine (5), were rapidly converted to DA (however, 2 was stable in plasma). Bioavailability, based on the AUC of DA, 1, 2, and 5 following oral administration to dogs, increased in the following order: 1, 2, 5, and DA. Thus, it was shown that the two protective groups introduced in 1 served to reduce the first-pass metabolism of the DA moiety in the absorption process. It was also confirmed that 1 is converted to 2 or DA in blood, liver, and intestine.
The effect of hydroxytyrosol and its nitroderivatives on catechol-O-methyl transferase activity in rat striatal tissue
Gallardo, Elena,Madrona, Andrs,Palma-Valds, Roco,Trujillo, Mariana,Espartero, Jos Luis,Santiago, Marti
, p. 61086 - 61091 (2014)
Hydroxytyrosol is a well-known phenolic compound with antioxidant properties that is found in virgin olive oil. Studies have shown that virgin olive oil has neuroprotective effects in rats; thus the purpose of the present study was to investigate the neuroprotective effect of hydroxytyrosol in rats. Additionally, this study aimed to investigate the neuroprotective potential of a homologous series of compounds with better lipophilic profiles in order to increase the assortment of compounds with a putative effect against Parkinson's disease (PD). In this context, the inhibition of catechol-O-methyl transferase (COMT) activity by hydroxytyrosol, nitrohydroxytyrosol, nitrohydroxytyrosol acetate and ethyl nitrohydroxytyrosol ether was investigated by measuring intracellular dopamine and its metabolite levels in the corpus striatum by high performance liquid chromatography (HPLC) with electrochemical detection. The animals received an acute (single dose; 20 mg kg-1; i.p.) or chronic (one daily dose for 5 days; 20 mg kg-1; i.p.) treatment of hydroxytyrosol and its nitroderivatives. For comparison, a commercial COMT inhibitor, Ro 41-0960, was also included. Our data show that acute and chronic systemic administration of these compounds produced a clear and statistically significant increase in the intracellular levels of dopamine and its metabolite, 3,4-dihydroxyphenylacetic acid. The increase in dopamine levels was very similar to the increase seen with Ro 41-0960 treatment. The effect of chronic treatment was stronger than that of acute treatment. With respect to the intracellular level of homovanillic acid, Ro 41-0960 produced a statistically significant decrease which it was not observed when hydroxytyrosol and its nitroderivatives were systemically administered. However, the chronic homovanillic acid treatment effect was stronger than the acute treatment. The results suggest that these compounds could inhibit COMT activity.
Toward a high added value compound 3, 4-dihydroxyphenylacetic acid by electrochemical conversion of phenylacetic acid
Trabelsi, Souhel Kallel,Dridi Gargouri, Olfa,Gargouri, Boutheina,Abdelhèdi, Ridha,Bouaziz, Mohamed
, p. 370 - 376 (2015)
Abstract The development of the effective procedure to recover the potentially high-added-value phenolic compound, 3,4-dihydroxyphenylacetic acid (3,4-DHPAA) was investigated using electrochemical conversion of phenylacetic acid (PAA). The proposed mechanism is based on the hypothesis of two-electron oxidation of PAA molecule leading to 3-hydroxyphenyl acetic acid. The latter underwent a second bi-electronic transfer by means of a radical cation, thus leading to the formation of the 2,5 dihydroxyphenylacetic (2,5-DHPAA) acid and 3,4-DHPAA as major products. The 3,4-DHPAA was synthesized by anodic oxidation of PAA at lead dioxide electrode and identified by cyclic voltammetry and spectrophotometry UV-visible. It was also confirmed by mass spectrophotometry using LC-MS/MS apparatus. According to their voltammetric behavior during electrolysis, the oxidation potential of 3,4-DHPAA was lower than that of PAA. The antioxidant activity was measured by DPPH assay, showing that the strongest antiradical activity was detected when the 3,4-DHPAA concentration was higher during electrolysis experiments.
p-Hydroxyphenylacetate 3-Hydroxylase as a Biocatalyst for the Synthesis of Trihydroxyphenolic Acids
Dhammaraj, Taweesak,Phintha, Aisaraphon,Pinthong, Chatchadaporn,Medhanavyn, Dheeradhach,Tinikul, Ruchanok,Chenprakhon, Pirom,Sucharitakul, Jeerus,Vardhanabhuti, Nontima,Jiarpinitnun, Chutima,Chaiyen, Pimchai
, p. 4492 - 4502 (2015)
Trihydroxyphenolic acids such as 3,4,5-trihydroxycinnamic acid (3,4,5-THCA) 4c and 2-(3,4,5-trihydroxyphenyl)acetic acid (3,4,5-THPA) 2c are strong antioxidants that are potentially useful as medicinal agents. Our results show that p-hydroxyphenylacetate (HPA) 3-hydroxylase (HPAH) from Acinetobacter baumannii can catalyze the syntheses of 3,4,5-THPA 2c and 3,4,5-THCA 4c from 4-HPA 2a and p-coumaric acid 4a, respectively. The wild-type HPAH can convert 4-HPA 2a completely into 3,4,5-THPA 2c within 100 min (total turnover number (TTN) of 100). However, the wild-type enzyme cannot efficiently synthesize 3,4,5-THCA 4c. To improve the efficiency, the oxygenase component of HPAH (C2) was rationally engineered in order to maximize the conversion of p-coumaric acid 4a to 3,4,5-THCA 4c. Results from site-directed mutagenesis studies showed that Y398S is significantly more effective than the wild-type enzyme for the synthesis of 3,4,5-THCA 4c; it can catalyze the complete bioconversion of p-coumaric acid 4a to 3,4,5-THCA 4c within 180 min (TTN ～ 23 at 180 min). The yield and stability of 3,4,5-THPA 2c and 3,4,5-THCA 4c were significantly improved in the presence of ascorbic acid. Thermostability studies showed that the wild-type C2 was very stable and remained active after incubation at 30, 35, and 40 °C for 24 h. Y398S was moderately stable because its activity was retained for 24 h at 30 °C and for 15 h at 35 °C. Transient kinetic studies using stopped-flow spectrophotometry indicated that the key improvement in the reaction of Y398S with p-coumaric acid 4a lies within the protein-ligand interaction. Y398S binds to p-coumaric acid 4a with higher affinity than the wild-type enzyme, resulting in a shift in equilibrium toward favoring the productive coupling path instead of the path leading to wasteful flavin oxidation.
