Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Isatin”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 289 records · Page 16Linked to original sources
PubMedDate not supplied

[Effect of oxidized indoles on monoamine oxidase activity in the rat brain mitochondria].

There is increasing evidence, that oxidized indoles, isatin, 5-hydroxyoxindole, 2-oxindole, play important regulatory functions in the brain. Isatin and 5-hydroxyoxindole share some common regulatory properties in cell cultures (Cane et al., 2000, BBRC, 276, 379), however, their effects on brain mitochondrial monoamine oxidases, a potential target for their action, have not been compared yet. Isatin acted as a rather selective monoamine oxidase B inhibitor, whereas 5-hydroxyoxindole was more selective monoamine oxidase A inhibitor, but it was less potent than that of 5-hydroxyisatin, a synthetic analogue of isatin.

Animals↗
PubMed1996

Anxiolytic activity of intraventricularly administered atrial natriuretic peptide in the rat.

Rat atrial natriuretic peptide (ANP) was investigated for putative anxiolytic activity in rats, following intracerebroventricular (ICV) administration. ANP in doses of 200 and 500 ng/rat induced significant anxiolysis, comparable with that of lorazepam (0.5 mg/kg, i.p.) in a variety of anxiety models (open-field, elevated plus-maze, social interaction, and novelty-induced feeding suppression tests). Isatin, an endogenous anxiogenic indole, shown to be an antagonist of ANP in vitro, significantly inhibited the anxiolytic effect of ANP in the elevated plus-maze test in subanxiogenic doses. The anxiolytic action of ANP was unaffected by flumazenil, a benzodiazepine receptor antagonist. Conversely, the anxiolytic action of lorazepam was antagonized by flumazenil but not by isatin. The data indicate that ANP may function as an endogenous anxiomodulator, which may act in conjunction with isatin independently of benzodiazepine receptors. These results strengthen the evidence for links between physiological systems involved in anxiety and those in natriuresis.

Animals↗
PubMed1996

Effects of some anxiogenic agents on rat brain monoamine oxidase (MAO) A and B inhibitory (tribulin) activity.

Anxiogenic agents, yohimbine, pentylenetetrazole (PTZ), quinine, bufotenine, flumazenil and isatin were administered (ip) to rats at doses known to induce anxiety in this species. All the drugs exhibited anxiogenic response on the elevated plus-maze and induced a parallel increase in endogenous brain monoamine oxidase (MAO) inhibitory (tribulin) activity. The intensity of the drug-induced anxiety was fairly well correlated with the magnitude of increase in the MAO A inhibitory component of tribulin but not so with its MAO B inhibitory component. Thus, in the doses used, the degree of anxiogenic activity was PTZ > yohimbine > bufotenine > quinine > isatin > flumazenil, in terms of % entries on the open arms of the maze, whereas the magnitude of endogenous MAO A inhibition was PTZ > yohimbine > bufotenine > quinine > flumazenil > isatin. The results indicate that the MAO A inhibitory component of tribulin, rather than its MAO B inhibitory component, may be responsible for the postulated function of tribulin as an endogenous marker of anxiety.

Animals↗
PubMed2004

Protein engineering of toluene ortho-monooxygenase of Burkholderia cepacia G4 for regiospecific hydroxylation of indole to form various indigoid compounds.

Previous work showed that random mutagenesis produced a mutant of toluene ortho-monooxygenase (TOM) of Burkholderia cepacia G4 containing the V106A substitution in the hydroxylase alpha-subunit (TomA3) that changed the color of the cell suspension from wild-type brown to green in rich medium. Here, DNA shuffling was used to isolate a random TOM mutant that turned blue due to mutation TomA3 A113V. To better understand the TOM reaction mechanism, we studied the specificity of indole hydroxylation using a spectrum of colored TOM mutants expressed in Escherichia coli TG1 and formed as a result of saturation mutagenesis at TomA3 positions A113 and V106. Colonies expressing these altered enzymes ranged in color from blue through green and purple to orange; and the enzyme products were identified using thin-layer chromatography, high performance liquid chromatography, and liquid chromatography-mass spectroscopy. Derived from the single TOM template, enzymes were identified that produced primarily isoindigo (wild-type TOM), indigo (A113V), indirubin (A113I), and isatin (A113H and V106A/A113G). The discovery that wild-type TOM formed isoindigo via C-2 hydroxylation of the indole pyrrole ring makes this the first oxygenase shown to form this compound. Variant TOM A113G was unable to form indigo, indirubin, or isoindigo (did not hydroxylate the indole pyrrole ring), but produced 4-hydroxyindole and unknown yellow compounds from C-4 hydroxylation of the indole benzene ring. Mutations at V106 in addition to A113G restored C-3 indole oxidation, so along with C-2 indole oxidation, isatin, indigo, and indirubin were formed. Other TomA3 V106/A113 mutants with hydrophobic, polar, or charged amino acids in place of the Val and/or Ala residues hydroxylated indole at the C-3 and C-2 positions, forming isatin, indigo, and indirubin in a variety of distributions. Hence, for the first time, a single enzyme was genetically modified to produce a wide range of colors from indole.

Base Sequence↗
PubMed1989

Ketopantoyl-lactone reductase from Candida parapsilosis: purification and characterization as a conjugated polyketone reductase.

Ketopantoyl-lactone reductase (2-dehydropantoyl-lactone reductase, EC 1.1.1.168) was purified and crystallized from cells of Candida parapsilosis IFO 0708. The enzyme was found to be homogeneous on ultracentrifugation, high-performance gel-permeation liquid chromatography and SDS-polyacrylamide gel electrophoresis. The relative molecular mass of the native and SDS-treated enzyme is approximately 40,000. The isoelectric point of the enzyme is 6.3. The enzyme was found to catalyze specifically the reduction of a variety of natural and unnatural polyketones and quinones other than ketopantoyl lactone in the presence of NADPH. Isatin and 5-methylisatin are rapidly reduced by the enzyme, the Km and Vmax values for isatin being 14 microM and 306 mumol/min per mg protein, respectively. Ketopantoyl lactone is also a good substrate (Km = 333 microM and Vmax = 481 mumol/min per mg protein). Reverse reaction was not detected with pantoyl lactone and NADP+. The enzyme is inhibited by quercetin, several polyketones and SH-reagents. 3,4-Dihydroxy-3-cyclobutene-1,2-dione, cyclohexenediol-1,2,3,4-tetraone and parabanic acid are uncompetitive inhibitors for the enzyme, the Ki values being 1.4, 0.2 and 3140 microM, respectively, with isatin as substrate. Comparison of the enzyme with the conjugated polyketone reductase of Mucor ambiguus (S. Shimizu, H. Hattori, H. Hata and H. Yamada (1988) Eur. J. Biochem. 174, 37-44) and ketopantoyl-lactone reductase of Saccharomyces cerevisiae suggested that ketopantoyl-lactone reductase is a kind of conjugated polyketone reductase.

Alcohol Oxidoreductases↗
PubMed1966

The metabolism of [2-14C] indole in the rat.

1. [2-(14)C]Indole has been synthesized from [(14)C]formate and o-toluidine via N[(14)C]-formyltoluidine. 2. When fed to rats, the (14)C of [(14)C]indole (dose 70-80mg./kg. body wt.) is fairly rapidly excreted, and in 2 days an average of 81% appears in the urine, 11% in the faeces and 2.4% as carbon dioxide in the expired air. 3. Radioactivity is excreted in the urine as indoxyl sulphate (50% of the dose), indoxyl glucuronide (11%), oxindole (1.4%), isatin (5.8%), 5-hydroxyoxindole conjugates (3.1%), N-formylanthranilic acid (0.5%) and unchanged indole (0.07%). The faeces contain indoxyl sulphate (0.4% of the dose) and indole (0.2%), but the major metabolites have not been identified. 4. Fed to rats with biliary cannulae an average of 5.6% of a dose of [(14)C]indole (20-60mg./kg. body wt.) is excreted in the bile in 2 days. Radioactivity is present as indoxyl sulphate (0.8% dose) and 5-hydroxyoxindole conjugates (0.6%). 5. Rats further metabolize indoxyl into N-formylanthranilic acid and anthranilic acid, and oxindole into 5-hydroxyoxindole. 6. With rat-liver microsomes plus supernatant under aerobic conditions, indole gives indoxyl, oxindole, possibly isatin, N-formylanthranilic acid and anthranilic acid, but under anaerobic conditions gives only oxindole. Similarly, under aerobic conditions, oxindole gives 5-hydroxyoxindole, anthranilic acid and o-aminophenylacetic acid. 7. Indole is metabolized by two pathways, one via indoxyl to isatin, N-formylanthranilic acid and anthranilic acid, and the other via oxindole to 5-hydroxyoxindole and possibly to o-aminophenylacetic and anthranilic acid. 8. The following new compounds are described: 4-hydroxy-2-nitrophenylacetic acid, 3-, 4- and 5-benzyloxy-2-nitrophenylacetic acid, 5- and 7-hydroxyoxindole and 5-aminoacridine indoxyl sulphate.

Animals↗
PubMed1973

Inhibition of RNA-dependent DNA polymerase of Rous sarcoma virus by thiosemicarbazones and several cations.

The RNA-dependent DNA polymerase of Rous sarcoma virus is inhibited by N-methyl isatin beta-thiosemicarbazone and by thiosemicarbazide, but not by semicarbazide. These inhibitors also inactivate, upon contact with the virion, the transforming ability of Rous sarcoma virus. Sulfhydryl donors, such as 2-mercapto-ethanol, can prevent these effects. The RNA-directed activity of the purified polymerase is inhibited to a greater degree than is the DNA-directed activity. Two cations, Cu(++) and Hg(++), can inhibit RNA-dependent DNA polymerase and inactivate the transforming ability of the virus. Synergism between N-methyl isatin beta-thiosemicarbazone and Cu(++) occurs, since treatment of the virus with a low dose of either N-methyl isatin beta-thiosemicarbazone or Cu(++) has little effect; however, when the two compounds are mixed together, significant inactivation occurs. This observation supports the hypothesis that the antiviral action of thiosemicarbazones is a function of their ability to act as a ligand for metallic ions. Several cations (Ag(+), Co(++), Zn(++), Cd(++), and Ni(++)) significantly inactivate the RNA-dependent DNA polymerase, but have little effect on the transforming ability. In view of this result, the conclusion that the enzyme activity is required for transformation remains open to question.

Animals↗
PubMed1991

Degradation of substituted indoles by an indole-degrading methanogenic consortium.

Degradation of indole by an indole-degrading methanogenic consortium enriched from sewage sludge proceeded through a two-step hydroxylation pathway yielding oxindole and isatin. The ability of this consortium to hydroxylate and subsequently degrade substituted indoles was investigated. Of the substituted indoles tested, the consortium was able to transform or degrade 3-methylindole and 3-indolyl acetate. Oxindole, 3-methyloxindole, and indoxyl were identified as metabolites of indole, 3-methylindole, and 3-indolyl acetate degradation, respectively. Isatin (indole-2,3-dione) was produced as an intermediate when the consortium was amended with oxindole, providing evidence that degradation of indole proceeded through successive hydroxylation of the 2- and 3-positions prior to ring cleavage between the C-2 and C-3 atoms on the pyrrole ring of indole. The presence of a methyl group (-CH3) at either the 1- or 2-position of indole inhibited the initial hydroxylation reaction. The substituted indole, 3-methylindole, was hydroxylated in the 2-position but not in the 3-position and could not be further metabolized through the oxindole-isatin pathway. Indoxyl (indole-3-one), the deacetylated product of 3-indolyl acetate, was not hydroxylated in the 2-position and thus was not further metabolized by the consortium. When an H atom or electron-donating group (i.e., -CH3) was present at the 3-position, hydroxylation proceeded at the 2-position, but the presence of electron-withdrawing substituent groups (i.e., -OH or -COOH) at the 3-position inhibited hydroxylation.

Biodegradation, Environmental↗
PubMedDate not supplied

[The structure and antihypoxic action of alpha-dicarbonyl compounds and their derivatives].

The protective action in hypoxic hypoxia of 29 synthetized alpha-dicarbonyl compounds were studied. In this series of substances the natihypoxic activity was found to be most marked in drugs whose redox potential amounted to 0.15--0.3 V and which displayed a high dehydrating activity. Such compounds include isatin, its 3-anyl, 3-thiosemicarbation of ethyl either, isatin-1 of acetic acid and acenaphthequinone. Substitution is position 1 and 3 of isatin can lead to the formation of active substances, whereas substitution in position 2 usually reduces the antihypoxic activity.

Animals↗
PubMed1998

Function of endogenous monoamine oxidase inhibitors (tribulin).

Recent research on tribulin [low molecular weight endogenous inhibitory activity of monoamine oxidase (MAO)] has confirmed that its level is increased in both human urine and rat tissues by stress or anxiety, and by anxiogenic drugs. However tribulin is now known to contain several different molecules. The raised inhibitory activity in rat tissues is selective for MAO-A. There is a parallel decrease in MAO-A activity ex vivo, suggesting a possible functional effect. Increase in endogenous MAO I may competitively inhibit the binding of irreversible MAO I drugs, and may also help to mediate some mood altering effects of other drugs, or procedures such as ECT. In human urine both MAO-A I and MAO-B I have been found to be increased in mild stress. Similar findings have been made with human saliva. Selective inhibitors of MAO-A have been identified from human urine, and pig brain, but it is not yet clear to what extent they account for the MAO-A I activity increased in stress. Isatin is an endogenous selective inhibitor of MAO-B (K1 approximately 3 microM). It has a distinct distribution in rat brain, with highest concentration in the hippocampus of 0.1 microgram/g. Its level is increased by pentylene tetrazole, and isatin is itself anxiogenic in rodent models. Its administration also increases monoamine levels in the brain. It is a potent antagonist of the ANP receptor, and it may act to link the control of monoamine function and natriuresis.

Animals↗
PubMed2004

Inhibition of brain mitochondrial monoamine oxidases by the endogenous compound 5-hydroxyoxindole.

5-Hydroxyoxindole is a recently identified endogenous compound. Its physiological role remains unclear but certain evidence exists, that it may share some regulatory properties with isatin, a known endogenous inhibitor of monoamine oxidase (MAO) type B (MAO-B). In this study several oxidized indoles were tested for their in vitro inhibition of MAO type A (MAO-A) and B of rat brain non-synaptic mitochondria. 5-Hydroxyoxindole was less potent MAO-A inhibitor (IC50 56.8 microM) than isatin (31.8 microM) and especially 5-hydroxyisatin (6.5 microM), but it was the only highly selective MAO-A inhibitor among the all compounds studied (IC50 MAO-A:IC50 MAO-B = 0.044). Thus, the in vitro data suggest that MAO-A may represent potential target for 5-hydroxyoxindole.

Animals↗
PubMed2004

A microtitre format assay for proline in human serum or plasma.

BACKGROUND: Recent studies have suggested that low serum proline concentration may be associated with low bone mineral density. However, further investigation of this association has been hampered by the lack of a relatively high throughput assay for proline in biological fluids. Here we report a sensitive and specific microtitre plate format assay for proline which exploits the chemical interaction between proline and isatin. METHODS: Human serum or plasma is deproteinised by incubation with sodium citrate buffer pH 4.1 at 95 degrees C, and the supernatant is reacted with isatin at 95 degrees C for 3 h. The resultant blue coloured product is quantitated sprectrophometrically. RESULTS: This assay yields a linear standard curve in the range 15 micromol/l to 1 mmol/l (r=0.998+/-0.002; n=8 determinations) with a sensitivity of 31+/-11 micromol/l. None of the other proteogenic amino acids are detected (<0.3% detection at 10 mmol/l) and the closely related metabolite hydroxyproline is only very weakly detected (3% detection at 10 mmol/l). Using human serum, the assay has linear dilution characteristics and a mean spike recovery of 107+/-5%. Repeated re-measurement of the same serum sample yields an intra-assay coefficient of variation (CV) of 4.8% and an inter-assay CV of 6.1%. CONCLUSIONS: This method provides the first reliable micro-titre format assay for proline in human serum.

Buffers↗
PubMed2003

Discovery of inhibitors that elucidate the role of UCH-L1 activity in the H1299 lung cancer cell line.

Neuronal ubiquitin C-terminal hydrolase (UCH-L1) has been linked to Parkinson's disease (PD), the progression of certain nonneuronal tumors, and neuropathic pain. Certain lung tumor-derived cell lines express UCH-L1 but it is not expressed in normal lung tissue, suggesting that this enzyme plays a role in tumor progression, either as a trigger or as a response. Small-molecule inhibitors of UCH-L1 would be helpful in distinguishing between these scenarios. By utilizing high-throughput screening (HTS) to find inhibitors and traditional medicinal chemistry to optimize their affinity and specificity, we have identified a class of isatin O-acyl oximes that selectively inhibit UCH-L1 as compared to its systemic isoform, UCH-L3. Three representatives of this class (30, 50, 51) have IC(50) values of 0.80-0.94 micro M for UCH-L1 and 17-25 micro M for UCH-L3. The K(i) of 30 toward UCH-L1 is 0.40 micro M and inhibition is reversible, competitive, and active site directed. Two isatin oxime inhibitors increased proliferation of the H1299 lung tumor cell line but had no effect on a lung tumor line that does not express UCH-L1. Inhibition of UCH-L1 expression in the H1299 cell line using RNAi had a similar proproliferative effect, suggesting that the UCH-L1 enzymatic activity is antiproliferative and that UCH-L1 expression may be a response to tumor growth. The molecular mechanism of this response remains to be determined.

Antineoplastic Agents↗
PubMed2006

An immunochemical approach to model and long-term suppression of depressive and anxiety behavior.

The inhibitor of monoaminooxydase isatin and the ligand of B-receptors cholecystokinin-4 play a significant role in the suppression and induction of depressive and anxiety states. We induced the formation of auto-antibodies to these compounds against their conjugates with antigen-carrier by immunization of white rats. The result was long-term (more than 2 months) stimulation of depressive and anxiety behavior after immunization to isatin and, in contrast, the suppression of such behavior after immunization to cholecystokinin. The perspective of immunochemical approach to long-term correction of behavior is discussed.

Animals↗
PubMed2003

Insights into the mode of inhibition of human mitochondrial monoamine oxidase B from high-resolution crystal structures.

Monoamine oxidase B (MAO-B) is an outer mitochondrial membrane-bound enzyme that catalyzes the oxidative deamination of arylalkylamine neurotransmitters and has been a target for a number of clinically used drug inhibitors. The 1.7-A structure of the reversible isatin-MAO-B complex has been determined; it forms a basis for the interpretation of the enzyme's structure when bound to either reversible or irreversible inhibitors. 1,4-Diphenyl-2-butene is found to be a reversible MAO-B inhibitor, which occupies both the entrance and substrate cavity space in the enzyme. Comparison of these two structures identifies Ile-199 as a "gate" between the two cavities. Rotation of the side chain allows for either separation or fusion of the two cavities. Inhibition of the enzyme with N-(2-aminoethyl)-p-chlorobenzamide results in the formation of a covalent N(5) flavin adduct with the phenyl ring of the inhibitor occupying a position in the catalytic site overlapping that of isatin. Inhibition of MAO-B with the clinically used trans-2-phenylcyclopropylamine results in the formation of a covalent C(4a) flavin adduct with an opened cyclopropyl ring and the phenyl ring in a parallel orientation to the flavin. The peptide bond between the flavin-substituted Cys-397 and Tyr-398 is in a cis conformation, which allows the proper orientation of the phenolic ring of Tyr-398 in the active site. The flavin ring exists in a twisted nonplanar conformation, which is observed in the oxidized form as well as in both the N(5) and the C(4a) adducts. An immobile water molecule is H-bonded to Lys-296 and to the N(5) of the flavin as observed in other flavin-dependent amine oxidases. The active site cavities are highly apolar; however, hydrophilic areas exist near the flavin and direct the amine moiety of the substrate for binding and catalysis. Small conformational changes are observed on comparison of the different inhibitor-enzyme complexes. Future MAO-B drug design will need to consider "induced fit" contributions as an element in ligand-enzyme interactions.

Catalytic Domain↗
PubMed2000

Potent and selective nonpeptide inhibitors of caspases 3 and 7 inhibit apoptosis and maintain cell functionality.

Caspases have been strongly implicated to play an essential role in apoptosis. A critical question regarding the role(s) of these proteases is whether selective inhibition of an effector caspase(s) will prevent cell death. We have identified potent and selective non-peptide inhibitors of the effector caspases 3 and 7. The inhibition of apoptosis and maintenance of cell functionality with a caspase 3/7-selective inhibitor is demonstrated for the first time, and suggests that targeting these two caspases alone is sufficient for blocking apoptosis. Furthermore, an x-ray co-crystal structure of the complex between recombinant human caspase 3 and an isatin sulfonamide inhibitor has been solved to 2.8-A resolution. In contrast to previously reported peptide-based caspase inhibitors, the isatin sulfonamides derive their selectivity for caspases 3 and 7 by interacting primarily with the S(2) subsite, and do not bind in the caspase primary aspartic acid binding pocket (S(1)). These inhibitors blocked apoptosis in murine bone marrow neutrophils and human chondrocytes. Furthermore, in camptothecin-induced chondrocyte apoptosis, cell functionality as measured by type II collagen promoter activity is maintained, an activity considered essential for cartilage homeostasis. These data suggest that inhibiting chondrocyte cell death with a caspase 3/7-selective inhibitor may provide a novel therapeutic approach for the prevention and treatment of osteoarthritis, or other disease states characterized by excessive apoptosis.

Amino Acid Chloromethyl Ketones↗
PubMed1988

A novel fungal enzyme, NADPH-dependent carbonyl reductase, showing high specificity to conjugated polyketones. Purification and characterization.

A novel enzyme which specifically catalyzes the reduction of conjugated polyketones was purified to homogeneity from cells of Mucor ambiguus AKU 3006. The enzyme has a strict requirement for NADPH and irreversibly reduces a number of quinones such as p-benzoquinone, alpha-naphthoquinone and acenaphthenequione. The enzyme also reduces polyketones such as isatin and ketopantoyl lactone, and their derivatives. The apparent Km values for isatin and ketopantoyl lactone are 49.9 microM and 714 microM, respectively. The reduction of ketopantoyl lactone proceeds stereospecifically to yield L-(+)-pantoyl lactone. The pro-S (A) hydrogen at C-4 of NADPH is transferred to the substrate. The enzyme is not a flavoprotein and consists of two polypeptide chains with an identical relative molecular mass of 27,500. Quercetin, dicoumarol and some SH reagents inhibit the enzyme activity. 3-Methyl-1,2-cyclopentanedione and 1,3-cyclohexanedione are uncompetitive inhibitors with Ki values of 80.9 microM and 64.5 microM, respectively, to ketopantoyl lactone.

4-Butyrolactone↗
PubMed1995

Catabolism of indole-3-acetic acid and 4- and 5-chloroindole-3-acetic acid in Bradyrhizobium japonicum.

Some strains of Bradyrhizobium japonicum have the ability to catabolize indole-3-acetic acid. Indoleacetic acid (IAA), 4-chloro-IAA (4-Cl-IAA), and 5-Cl-IAA were metabolized to different extents by strains 61A24 and 110. Metabolites were isolated and analyzed by high-performance liquid chromatography and conventional mass spectrometry (MS) methods, including MS-mass spectroscopy, UV spectroscopy, and high-performance liquid chromatography-MS. The identified products indicate a novel metabolic pathway in which IAA is metabolized via dioxindole-3-acetic acid, dioxindole, isatin, and 2-aminophenyl glyoxylic acid (isatinic acid) to anthranilic acid, which is further metabolized. Degradation of 4-Cl-IAA apparently stops at the 4-Cl-dioxindole step in contrast to 5-Cl-IAA which is metabolized to 5-Cl-anthranilic acid.

Chromatography, High Pressure Liquid↗