chiniofon and 4-hydroxyquinoline

The synthesis of alkyl 2-(4-hydroxyquinolin-2-yl) acetates and 1-phenyl-4-(phenylamino)pyridine-2,6(1

Topics: Adenocarcinoma; Antineoplastic Agents; Benzylidene Compounds; Colonic Neoplasms; Cytotoxins; Doxorubicin; Humans; Hydroxyquinolines

Kynurenic acid (KNA) and 4-hydroxyquinoline (4HQN) are photochemically active products of tryptophan catabolism that readily react with tryptophan (Trp) and tyrosine (Tyr) after optical excitation. Recently, transient absorption experiments have shown that at neutral pH Trp reacts with triplet KNA

Topics: Electron Transport; Hydrogen-Ion Concentration; Hydroxyquinolines; Kynurenic Acid; Molecular Dynamics Simulation; Tryptophan; Tyrosine

The present study investigates the human monoamine oxidase (MAO) inhibition properties of a series of twelve 2-heteroarylidene-1-tetralone derivatives. Also included are related cyclohexylmethylidene, cyclopentylmethylidene and benzylidene substituted 1-tetralones. These compounds are related to the 2-benzylidene-1-indanone class of compounds which has previously been shown to inhibit the MAOs, with specificity for the MAO-B isoform. The target compounds were synthesised by the Claisen-Schmidt condensation between 7-methoxy-1-tetralone or 1-tetralone, and various aldehydes, under acid (hydrochloric acid) or base (potassium hydroxide) catalysis. The results of the MAO inhibition studies showed that the 2-heteroarylidene-1-tetralone and related derivatives are in most instances more selective inhibitors of the MAO-B isoform compared to MAO-A. (2E)-2-Benzylidene-7-methoxy-3,4-dihydronaphthalen-1(2 H)-one (IC

Topics: Benzylidene Compounds; Enzyme Assays; Humans; Hydroxyquinolines; Inhibitory Concentration 50; Kynuramine; Molecular Structure; Monoamine Oxidase; Monoamine Oxidase Inhibitors; Structure-Activity Relationship; Tetralones

Recent publications report in vitro activity of quinolone 3-esters against the bc1 protein complex of Plasmodium falciparum and the parasite. Docking studies performed in silico at the yeast Qo site established a key role for the 4-oxo and N-H groups in drug-target interactions. Thus, the possibility of 4-oxoquinoline/4-hydroxyquinoline tautomerism may impact in pharmacologic profiles and should be investigated. We describe the synthesis, structure, photochemistry, and activity against multidrug-resistant P. falciparum strain Dd2 of ethyl 4-oxo-7-methylquinoline-3-carboxylate (7Me-OQE) and ethyl 4-hydroxy-5-methylquinoline-3-carboxylate (5Me-HQE), obtained from diethyl 2-[((3-methylphenyl)amino)methylene]malonate. Theoretically (B3LYP/6-311++G(d,p)), 5Me-HQE and 7Me-OQE show clear preference for the hydroxyquinoline form. The difference between the lowest energy hydroxyquinoline and quinolone forms is 27 and 38 kJ mol(-1), for 5Me-HQE and 7Me-OQE, respectively. Calculations of aromaticity indexes show that in 5Me-HQE both rings are aromatic, while in the corresponding oxo tautomers the nitrogen-containing ring is essentially non-aromatic. The structure of monomeric 5Me-HQE was studied using matrix isolation coupled to FTIR spectroscopy. No traces of 4-oxoquinoline tautomers were found in the experimental IR spectra, revealing that the species present in the crystal, 5Me-HQE·HCl, was lost HCl upon sublimation but did not tautomerize. Continuous broadband irradiation (λ > 220 nm; 130 min) of the matrix led to only partial photodecomposition of 5Me-HQE (ca. 1/3).

Topics: Antimalarials; Hydroxyquinolines; Malonates; Molecular Structure; Oxyquinoline; Photochemistry; Quinolines; Quinolones; Spectroscopy, Fourier Transform Infrared

In the present contribution, we have explored ground and excited state spectroscopic properties of an antiexcitotoxic and anticonvulsant drug, Kynurenic acid (KA), through steady-state absorption, emission and time-resolved emission spectroscopy and quantum chemical calculations. The main focus of this article is to illustrate the effects of various parameters such as the nature of the solvents and pH of the medium on the spectral properties of KA which confirms the presence of different neutral and ionic species in the ground and excited states. The molecule KA exists mainly as keto- or anionic form in the ground state, whereas the main contribution of its emission is arising from the keto tautomer in the excited state. Quantum chemical calculations by Density Functional Theory (DFT) method has been effectively employed to correlate the experimental findings. The ground and excited state properties of KA ascertained by means of experimental and theoretical method reveal that it resembles well with other two compounds, 4-hydroxyquinoline and xanthurenic acid formed by the decomposition of UV filters.

Topics: Hydrogen-Ion Concentration; Hydroxyquinolines; Kynurenic Acid; Models, Molecular; Photosensitizing Agents; Quantum Theory; Spectrometry, Fluorescence; Spectrophotometry, Ultraviolet; Xanthurenates

Naturally occurring quinolone and quinolone-like compounds, such as quinine, 2-hydroxyquinoline, 4-hydroxyquinoline, and 2-heptyl-3-hydroxy-4(1H)-quinolone, increased expression of qnrS1 in Escherichia coli 2.3- to 11.2-fold, similar to the synthetic quinolone ciprofloxacin. In contrast, chromosomal qnrVS1 of Vibrio splendidus was not induced by these compounds. Molecules associated with quorum sensing, such as N-3-hydroxybutyryl-homoserine lactone (HSL), N-hexanoyl-HSL, and N-3-(oxododecanoyl)-HSL, did not show an induction effect on either qnrS1 or qnrVS1 at the tested concentrations.

Topics: Anti-Bacterial Agents; Bacterial Proteins; Enzyme Induction; Escherichia coli; Escherichia coli Proteins; Hydroxyquinolines; Microbial Sensitivity Tests; Plasmids; Pseudomonas aeruginosa; Quinine; Quinolones; Quorum Sensing; Vibrio

The study by Dulcey and colleagues in this issue of Chemistry & Biology changes our perception of the pathway of 2-alkyl-4-hydroxyquinoline biosynthesis by the opportunistic pathogen Pseudomonas aeruginosa and suggests that the biosynthetic protein complex PqsBC is a potential antibacterial target.

Topics: Alkylation; Anti-Bacterial Agents; Bacterial Proteins; Biosynthetic Pathways; Drug Discovery; Humans; Hydroxyquinolines; Molecular Targeted Therapy; Pseudomonas aeruginosa; Pseudomonas Infections

A series of novel two-dimensional (2D) lanthanide coordination polymers with 4-hydroxyquinoline-2-carboxylate (H(2)hqc) ligands, [Ln(Hhqc)(3)(H(2)O)](n)·3nH(2)O (Ln = Eu (1), Tb (2), Sm (3), Nd (4), and Gd (5)) and [Ln(Hhqc)(ox)(H(2)O)(2)](n) (Ln = Eu (6), Tb (7), Sm (8), Tm (9), Dy (10), Nd (11), Yb (12), and Gd (13); H(2)ox = oxalic acid), have been synthesized under hydrothermal conditions. Complexes 1-5 are isomorphous, which can be described as a two-dimensional (2D) hxl/Shubnikov network based on Ln(2)(CO(2))(4) paddle-wheel units, and the isomorphous complexes 6-13 feature a 2D decker layer architecture constructed by Ln-ox infinite chains cross-linked alternatively by bridging Hhqc(-) ligands. The room-temperature photoluminescence spectra of complexes Eu(III) (1 and 6), Tb(III) (2 and 7), and Sm(III) (3 and 8) exhibit strong characteristic emissions in the visible region, whereas Nd(III) (4 and 11) and Yb(III) (12) complexes display NIR luminescence upon irradiation at the ligand band. Moreover, the triplet state of H(2)hqc matches well with the emission level of Eu(III), Tb(III), and Sm(III) ions, which allows the preparation of new optical materials with enhanced luminescence properties.

Topics: Carboxylic Acids; Crystallography, X-Ray; Drug Stability; Hydroxyquinolines; Lanthanoid Series Elements; Ligands; Light; Luminescence; Organometallic Compounds; Photochemical Processes; Polymers; Temperature

An LC-MS/MS method, using positive mode electrospray ionization, for the simultaneous, quantitative and targeted profiling of the N-acyl-L-homoserine lactone (AHL) and 2-alkyl 4-(1H)-quinolone (AQ) families of bacterial quorum-sensing signaling molecules (QSSMs) is presented. This LC-MS/MS technique was applied to determine the relative molar ratios of AHLs and AQs produced by Pseudomonas aeruginosa and the consequences of mutating individual or multiple QSSM synthase genes (lasI, rhlI, pqsA) on AHL and AQ profiles and concentrations. The AHL profile of P. aeruginosa was dominated by N-butanoyl-L-homoserine lactone (C4-HSL) with lesser concentrations of N-hexanoyl-L-homoserine lactone (C6-HSL) and 3-oxo-substituted longer chain AHLs including N-(3-oxodecanoyl)-L-homoserine lactone (3-oxo-C10-HSL) and N-(3-oxododecanoyl)-L-homoserine lactone (3-oxo-C12-HSL). The AQ profile of P. aeruginosa comprised the C7 and C9 long alkyl chain AQs including 2-heptyl-4-hydroxyquinoline (HHQ), 2-nonyl-4-hydroxyquinoline, the "pseudomonas quinolone signal" (2-heptyl-3-hydroxy-4-quinolone) and the N-oxides, 2-heptyl-4-hydroxyquinoline N-oxide and 2-nonyl-4-hydroxyquinoline N-oxide. Application of the method showed significant effects of growth medium type on the ratio and the nature of the QSSMs synthesized and the dramatic effect of single, double and triple mutations in the P. aeruginosa QS synthase genes. The LC-MS/MS methodology is applicable in organisms where either or both AHL and AQ QSSMs are produced and can provide comprehensive profiles and concentrations from a single sample.

Topics: 4-Butyrolactone; Bacterial Proteins; Chromatography, High Pressure Liquid; Hydroxyquinolines; Mutation; Pseudomonas aeruginosa; Quorum Sensing; Tandem Mass Spectrometry

Overexpression of efflux pumps is an important mechanism by which bacteria evade the effects of substrate antimicrobial agents. Inhibition of such pumps is a promising strategy to circumvent this resistance mechanism. NorA is a Staphylococcus aureus efflux pump that confers reduced susceptibility to many structurally unrelated agents, including fluoroquinolones, resulting in a multidrug resistant phenotype. In this work, a series of 2-phenyl-4(1H)-quinolone and 2-phenyl-4-hydroxyquinoline derivatives, obtained by modifying the flavone nucleus of known efflux pump inhibitors (EPIs), were synthesized in an effort to identify more potent S. aureus NorA EPIs. The 2-phenyl-4-hydroxyquinoline derivatives 28f and 29f display potent EPI activity against SA-1199B, a strain that overexpresses norA, in an ethidium bromide efflux inhibition assay. The same compounds, in combination with ciprofloxacin, were able to completely restore its antibacterial activity against both S. aureus SA-K2378 and SA-1199B, norA-overexpressing strains.

Topics: Anti-Bacterial Agents; Bacterial Proteins; Ciprofloxacin; Drug Synergism; Flavones; Hydroxyquinolines; Microbial Sensitivity Tests; Models, Chemical; Molecular Structure; Multidrug Resistance-Associated Proteins; Mutation; Species Specificity; Staphylococcus aureus; Structure-Activity Relationship

Electrochemically induced catalytic multicomponent transformation of isatins, 4-hydroxyquinolin-2(1H)-one and malononitrile in ethanol in an undivided cell in the presence of sodium bromide as an electrolyte results in the formation of spirooxindoles with fused functionalized indole-3,4'-pyrano[3,2-c]quinoline] scaffold in 75-91% substance yields and 500-600% current yield. The developed efficient electrocatalytic approach to medicinally relevant [indole-3,4'-pyrano[3,2-c]quinoline] scaffold is beneficial from the viewpoint of diversity-oriented large-scale processes and represents a novel example of facile environmentally benign synthetic concept for electrocatalytic multicomponent reactions.

Topics: Catalysis; Cyclization; Efficiency; Electrochemical Techniques; Heterocyclic Compounds; Hydroxyquinolines; Indoles; Isatin; Macromolecular Substances; Models, Biological; Nitriles; Quinolones; Spiro Compounds

A comparative study for selective glucosylation of N-unsubstituted 4-hydroxyquinolin-2(1H)-ones into 4-(tetra-O-acetyl-beta-D-glucopyranosyloxy)quinolin-2(1H)-ones is reported. Four glycosyl donors including tetra-O-acetyl-alpha-D-glucopyranosyl bromide, beta-D-glucose pentaacetate, glucose tetraacetate and tetra-O-acetyl-alpha-D-glucopyranosyl trichloroacetimidate were tested, along with different promoters and reaction conditions. The best results were obtained with tetra-O-acetyl-alpha-D-glucopyranosyl bromide with Cs(2)CO(3) in CH(3)CN. In some cases the 4-O-glucosylation of the quinolinone ring was accompanied by 2-O-glucosylation yielding the corresponding 2,4-bis(tetra-O-acetyl-beta-D-glucopyranosyloxy)quinoline. Next, 4-(tetra-O-acetyl-beta-D-glucopyranosyloxy)quinolin-2(1H)-ones were deacetylated into 4-(beta-D-glucopyranosyloxy)quinolin-2(1H)-ones with Et(3)N in MeOH. In some instances the deacetylation was accompanied by the sugar-aglycone bond cleavage. Structure elucidation, complete assignment of proton and carbon resonances as well as assignment of anomeric configuration for all the products under investigation were performed by 1D and 2D NMR spectroscopy.

Topics: Glycosylation; Hydroxyquinolines; Magnetic Resonance Spectroscopy; Molecular Structure

Two multivariate studies, a PCA-SAR and a PLS-QSAR, of 3-aryl-4-hydroxyquinolin-2(1H)-one derivatives described as type I fatty acid synthase (FAS) inhibitors, are presented in this work. The variable selection was performed with the Fisher's weight and Ordered Predictors Selection (OPS) algorithm, respectively. In the PCA, a separation between active and inactive compounds was obtained by six descriptors (topological and geometrical). The PLS model presented five descriptors and two Latent Variables. Leave-N-out cross validation and y-randomization test showed that the model presented robustness and no chance correlation, respectively, and the descriptors indicated that the FAS inhibition depends on electronic distribution of the investigated compounds. The model obtained in this study may provide a guidance for proposition of new FAS inhibitors.

Topics: Enzyme Inhibitors; Fatty Acid Synthase, Type I; Humans; Hydroxyquinolines; Models, Molecular; Molecular Structure; Stereoisomerism; Structure-Activity Relationship

The reaction of 1-methoxy-1,3-bis(trimethylsilyloxy)-1,3-butadiene with 2-methoxybenzoyl chlorides afforded 3,5-diketoesters which were transformed, by treatment with boron tribromide, into functionalized 2-hydroxychroman-4-ones or chromones. The reaction of 1-methoxy-1,3-bis(trimethylsilyloxy)-1,3-butadiene with 2-nitrobenzoyl chlorides and subsequent reduction of the nitro group afforded functionalized 4-hydroxyquinolines. Their tautomeric equilibrium was studied by NMR spectroscopy and by computational methods.

Topics: Butadienes; Catalysis; Chromones; Hydroxyquinolines; Molecular Structure; Nitrobenzoates; Trimethylsilyl Compounds

UV irradiation of aqueous 4-hydroxyquinoline (4HQN) solutions results in the formation of the triplet states with the quantum yields 30%, 35%, and 7.5% in acidic, neutral, and basic solutions, respectively. In neutral solutions, the keto form is the major tautomeric structure for ground, excited singlet and triplet states of 4HQN. Triplet 4HQN reacts with amino acids tryptophan and tyrosine and with antioxidant ascorbate via the mechanism of electron transfer. The individual experimental and calculated UV-Vis spectra of different acid-base forms of 4HQN in the ground and triplet excited states, as well as reduced and oxidized forms of 4HQN, are reported. Under intense laser irradiation 4HQN undergoes biphotonic ionization, the excited singlet state being the precursor for photoionization.

Topics: Absorption; Electrons; Hydrogen-Ion Concentration; Hydroxyquinolines; Kinetics; Lasers; Photolysis; Quantum Theory; Spectrometry, Fluorescence

Total monoamine oxidase activity was investigated in the pineal gland (epiphysis) and in three brain structures with the use of spectrophotometric method based on kynuramine oxidative deamination, the product (4-hydroxyquinoline) formation being detected at 327 nm. Female Wistar rats used for the experiment were 1.5-2, 4-5 and over 12 months old. In the pineal gland, olfactory tubercle cortex and median eminence (with surrounding tissue) the lowest activities (nmol/min per mg of the protein, M +/- m) were found in the group of rats aged 4-5 months (1.20 +/- 0.11; 0.62 +/- 0.05 and 4.36 +/- 0.25, respectively), whereas in the medial preoptic area the lowest activity was found in rats aged 1.5-2 months (1.55 +/- 0.11). In all of the four structures the highest activities were found in the group of rats aged over 12 months (2.17 +/- 0.40; 0.8 +/- 0.04; 6.61 +/- 0.56 and 2,01 +/- 0.15, respectively). The data obtained agree with the hypothesis that low monoamine concentrations in some brain areas (including some hypothalamic structures) of aged rats, are due to, at least partly, an increase in monoamine oxidase activity.

Topics: Aging; Animals; Brain; Female; Hydroxyquinolines; Kynuramine; Monoamine Oxidase; Olfactory Pathways; Pineal Gland; Rats; Rats, Wistar

High-affinity iodine- and ethyl-C-5 substituted analogs of 4-hydroxy-3-(3-[11C]methoxyphenyl)-2(1H)-quinolone ([11C]4HQ) were synthesized as new positron emission tomography radioligands for the glycine-binding sites of the N-methyl-d-aspartate (NMDA) ion channel. Although both radioligands showed high in vitro specific binding to rat brain slices, their binding characteristics were quite different from each other. 5-Ethyl-[11C]4HQ (5Et-[11C]4HQ) showed higher in vitro binding in the forebrain regions than in the cerebellum, bindings that were strongly inhibited by both glycine-site agonists and antagonists. In contrast, 5-iodo-[11C]4HQ (5I-[11C]4HQ) showed a homogeneous in vitro binding throughout the brain, which was inhibited by antagonists but not by agonists. This difference in in vitro binding between 5Et-[11C]4HQ and 5I-[11C]4HQ was quite similar to that previously observed between [11C]L-703,717 and [11C]4HQ, both glycine-site antagonists. In vivo brain uptakes of these 11C-labeled 4-hydroxyquinolones were examined in mice. Initial brain uptakes of 5Et- and 5I-[11C]4HQ at 1 min after intravenous injections were comparable to that of [11C]4HQ, but they were 1.3-2.1 times higher than that of [11C]L-703,717. The treatment with an anticoagulant, warfarin, only slightly increased the initial uptakes of [11C]4HQ and 5Et-[11C]4HQ in contrast to [11C]L-703,717. The in vivo regional brain distributions were slightly different between the two radioligands. Pretreatment with nonradioactive ligand (2 mg/kg) slightly inhibited the binding of 5Et-[11C]4HQ (16-36% inhibition) but not that of 5I-[11C]4HQ. In this study, it was found that a small structural change in [11C]4HQ resulted in a major change in binding characteristics and distributions, suggesting the existence of two binding sites for [11C]4-hydroxyquinolones on the NMDA ion channel - agonist-sensitive and agonist-insensitive (or antagonist-preferring) sites.

Topics: Animals; Anticoagulants; Binding Sites; Binding, Competitive; Brain; Carbon Radioisotopes; Glycine; Hydroxyquinolines; Ion Channels; Mice; Positron-Emission Tomography; Radioligand Assay; Receptors, N-Methyl-D-Aspartate; Tissue Distribution; Warfarin

The activity of a novel enaminone derivative of 4-hydroxyquinoline, BDHQ, was screened for its effectiveness against murine schistosomiasis by electron microscopy and parasitologic studies. The correlation of these studies with serum levels of IFN-gamma and IgE is described. Two groups of 10 mice each were treated with different doses of BDHQ, and their results were correlated with the control and praziquantel (PZQ)-treated groups. Parasitologic study revealed significant reduction in mature worms and tissue egg loads in BDHQ- and PZQ-treated groups, whereas immature worms revealed significant reduction in BDHQ groups only. The group treated with a higher dose of BDHQ showed significant reductions in intestinal ova count when compared with the PZQ-treated group. Ultrastructural examination of the worm revealed significant degeneration of the spines and tegument in all treated groups, while the genital system was affected in BDHQ-treated groups only. BDHQ showed considerable effect on cellular activation where serum levels of IFN-gamma were significantly increased in comparison to control, while anti-soluble worm antigen preparation (SWAP) IgE was significantly increased in comparison to both the control and PZQ-treated groups. Ultrastructural examination revealed cellular activation in buffy coat and the liver in both the BDHQ- and PZQ-treated groups in comparison to the untreated one, whereas in the bone marrow and spleen, evidence of cellular activation was remarkable in the BDHQ-treated groups. In conclusion, BDHQ exhibits high levels of activity against adult and juvenile stages of these parasites, which may be due to its mixed cellular and humoral immunologic mechanisms, as demonstrated by the significant increase of serum levels of IgE and IFN-gamma shown on electron microscopy. Therefore, our results support the comparative advantage that BDHQ has over PZQ.

Topics: Animals; Female; Hydroxyquinolines; Male; Mice; Parasite Egg Count; Praziquantel; Schistosoma mansoni; Schistosomiasis mansoni

A highly efficient method utilizing liquid chromatography with tandem mass spectrometry (LC/MS/MS) was developed and employed for high-throughput screening of compounds for monoamine oxidase (MAO) inhibition. The method used kynuramine as a common substrate for both MAO-A and MAO-B in incubations, and the 4-hydroxyquinoline (4-HQ) resulting from deamination of kynuramine followed by intramolecular condensation was analyzed using LC/MS/MS; formation of 4-HQ was used as the marker of MAO activity to evaluate the effects of test compounds. Isocratic liquid chromatography was applied to reduce the run time to 2 min. Because of the high specificity and sensitivity of detection of 4-HQ by LC/MS/MS, this method was able to use MAO enzymes at very low concentrations and to perform short incubations; as a result, consumable cost was minimized, and sample preparations were completely avoided. The inhibition data are highly reproducible, and the IC(50) values determined by the method are in good agreement with literature values. The results suggest that this method is very robust and can be used as a generic approach to screen for MAO inhibitors in drug discovery.

Topics: Chromatography, High Pressure Liquid; Humans; Hydroxyquinolines; Kynuramine; Monoamine Oxidase; Monoamine Oxidase Inhibitors; Sensitivity and Specificity; Spectrometry, Mass, Electrospray Ionization

7-Chloro-4-hydroxyquinoline (CQ) is an antitumor drug but its efficiency is not very satisfactory. This fact motivates us to study the relationship between the structure of 4-hydroxyquinoline with various substituent and its antioxidant effect against free-radical-initiated peroxidation: the hemolysis of human erythrocyte initiated thermally by water-soluble initiator, 2,2'-azobis (2-amidinopropane hydrochloride) (AAPH), acts as an experimental system. 7-Fluoro-4-hydroxyquinoline (FQ) and CQ can be synthesized by decarboxylation of 7-fluoro-4-hydroxyquinoline-3-carboxylic acid (FQCA) and 7-chloro-4-hydroxyquinoline-3-carboxylic acid (CQCA), respectively, and FQCA and CQCA are prepared by hydrolysis of ethyl 7-fluoro-4-hydroxyquinoline-3-carboxylate (FQCE) and ethyl 7-chloro-4-hydroxyquinoline-3-carboxylate (CQCE), respectively. The inhibitory concentration of 50% inhibition (IC(50)) of AAPH-induced hemolysis of the erythrocyte has been studied and found that all these chemicals dissolved in dimethyl sulfoxide (DMSO) can inhibit the free-radical-induced peroxidation. To clarify the relationship between the distributive status of the chemicals and their antioxidant effect, the chemical has been dissolved in the vesicle of dipalmitoyl phosphatidylcholine (DPPC) by sonication and suspended in the reaction system. It is found that FQCE, CQCE, FQCA and CQCA act as prooxidants either used alone or used in combination with alpha-tocopherol (TOH), demonstrating that FQCE, CQCE, FQCA and CQCA play a prooxidative role when they are packaged in the DPPC vesicle. This can be understood that the electron-attracting group, i.e. -COOC(2)H(5), -COOH, at the ortho position to the hydroxy group of quinoline makes the phenoxy radical of quinoline derivatives active by attracting negative charge from the electron-deficient radical site. These unstable free radicals preserved in DPPC vesicle can initiate additional propagation of lipid peroxidation and cause hemolysis. However, FQ and CQ without electron-attracting group are antioxidants even in DPPC vesicle either used alone, or mixed with TOH. Moreover, the antioxidative activity of FQ is much better than CQ either used alone or in combination with TOH, indicating that FQ has the potential to replace CQ to be an antioxidant drug. Therefore, the antioxidant/prooxidant effect is not only correlated with the molecular structure but also the distributive status in the reaction system.

Topics: 1,2-Dipalmitoylphosphatidylcholine; alpha-Tocopherol; Amidines; Antioxidants; Erythrocytes; Free Radicals; Hemolysis; Humans; Hydroxyquinolines; Models, Chemical; Oxidants; Time Factors

Despite the fact that hydergine has been used in the treatment of dementia for many years, its mechanism of action is still not clear. Current studies imply that the major effect of hydergine may be the modulation of synaptic neurotransmission rather than solely increasing blood flow as was once thought. A prominent feature that accompanies aging is an increase in monoamine oxidase (MAO) levels which results in decreased availability of catecholamines in the synaptic cleft. The aim of this study was to determine the effects of hydergine on the MAO activity in different brain regions (cortex, olfactory bulb, hypothalamus, hippocampus, striatum, cerebellum) of old (30 months) and adult (12 months) male Sprague-Dawley rats. In cortex and olfactory bulb MAO levels were higher in the aged group. In hippocampus and hypothalamus hydergine treatment caused significant decreases in MAO levels. An interaction between age and hydergine treatment was observed in the hypothalamus, hippocampus and cerebellum. The hydergine effect was more pronounced in the aged group in the hypothalamus and cerebellum, and more pronounced in the adult in the hippocampus. Our findings imply that increased brain MAO activity in aging can be modified by hydergine treatment in some brain regions.

Topics: Aging; Animals; Brain; Ergoloid Mesylates; Hydroxyquinolines; Kynuramine; Male; Monoamine Oxidase; Nootropic Agents; Rats; Rats, Sprague-Dawley; Spectrometry, Fluorescence

A fluorimetric assay for monamine oxidase that uses kynuramine as the substrate is described. This method is more economic, rapid, reproducible, and sensitive than other similar procedures. Its validity has been confirmed by the study of the subcellular distribution, the effects of inhibitors, and the kinetics of enzyme activity. Previous reports of substrate inhibition by kynuramine may have to be reassessed in the light of evidence presented here.

Topics: Animals; Brain; Clorgyline; Hydroxyquinolines; Kinetics; Kynuramine; Male; Monoamine Oxidase; Monoamine Oxidase Inhibitors; Rats; Rats, Inbred Strains; Selegiline; Spectrometry, Fluorescence

1. Perch brain homogenates were incubated in vitro and monoamine oxidase (MAO) activity was determined fluorometrically, using a kynuramine substrate. 2. Clorgyline, harmaline and deprenyl inhibited MAO activity in a concentration-related manner, with single sigmoid inhibition curves, and the type A inhibitors harmaline and clorgyline were more effective than the type B inhibitor deprenyl. 3. Two types of inhibition were recognized in vitro; a fast-onsetting inhibition, similar to that produced by a reversible inhibitor, and a slow-onsetting inhibition, which is time- and concentration-dependent and presumably represents inactivation of the enzyme.

Topics: Animals; Brain; Clorgyline; Female; Fishes; Harmaline; Hydroxyquinolines; In Vitro Techniques; Male; Monoamine Oxidase Inhibitors; Selegiline; Time Factors

Topics: Hydroxyquinolines; Metabolism; Pseudomonas aeruginosa; Quinolines; Research

Topics: Chlorophyll; Chloroplasts; Hydroxyquinolines; Light; Oxides; Quinolines

Topics: Bacteria; Cytochromes; Dihydrostreptomycin Sulfate; Humans; Hydroxyquinolines; Myocardium; Oxides; Pseudomonas aeruginosa; Quinolines; Streptomycin

Topics: Hydroxyquinolines

Topics: Dermatologic Agents; Hydroxyquinolines; Quinolines

Topics: Hydroxyquinolines; Oxyquinoline; Quinolines

Topics: Hydroxyquinolines; Quinolines; Sulfur

Topics: Esters; Hydroxyquinolines; Quinolines

Topics: Acrylates; Esters; Hydroxyquinolines; Quinolines

Topics: Anilides; Hydroxyquinolines; Quinolines

Topics: Amidines; Hydroxyquinolines; Quinolines

Topics: Acids; Hydroxyquinolines; Quinolines

Topics: Hydroxyquinolines; Quinolines

Topics: Hydroxyquinolines; Quinolines

Topics: Hydroxyquinolines; Quinolines