Disease relevance of Isatin

• The commensal Alteromonas sp. bacteria protect shrimp embryos from fungal infection by producing and liberating the antifungal metabolite 2,3-indolinedione [1].
• An isatin-beta-thiosemicarbazone-resistant vaccinia virus containing a mutation in the second largest subunit of the viral RNA polymerase is defective in transcription elongation [2].
• CSF isatin is elevated in bulimia nervosa [3].
• Using a combinatorial method, variants of the basic isatin-beta-thiosemicarbazone structure were prepared and examined for cytotoxicity and antiviral activity in vaccinia virus- and cowpox virus-infected human cells [4].
• Further study showed that, unlike the irreversible covalent binding of isatin derivatives to human rhinovirus 3C protease, the compounds tested in this study are all noncovalent reversible inhibitors [5].

Psychiatry related information on Isatin

• Urinary tribulin output in patients with panic attacks [6].
• Increased urinary tribulin output in generalised anxiety disorder [7].
• Tribulin in post-traumatic stress disorder [8].
• The effects of acute food deprivation and acute cold exposure on 24-hr urinary isatin excretion in rats and a mechanism responsible for changes in urinary isatin excretion during stress were investigated [9].
• Augmentation of rat brain endogenous monoamine oxidase inhibitory activity (tribulin) by electroconvulsive shock [10].

High impact information on Isatin

• In contrast, the reversible competitive inhibitor isatin binds to all known MAO B and MAO A with similar affinities [11].
• The human MAO B I199F mutant protein of MAO B binds to isatin (K(i) = 3 microM) but not to the three inhibitors listed above [11].
• Superoxide generated using xanthine oxidase and acetaldehyde also converted indigo carmine to isatin sulfonic acid in a reaction that was completely inhibited by superoxide dismutase and unaffected by catalase [12].
• Stimulated neutrophils promoted the loss of indigo carmine and formation of isatin sulfonic acid in a reaction that was completely inhibited by superoxide dismutase [12].
• Superoxide converts indigo carmine to isatin sulfonic acid: implications for the hypothesis that neutrophils produce ozone [12].

Chemical compound and disease context of Isatin

• The viral protein synthesis pattern observed in vaccinia virus-infected cells treated with the drug isatin-beta-thiosemicarbazone was strikingly similar to that observed in ts22-infected cells at the nonpermissive temperature (J. Cooper, B. Moss, and E. Katz, Virology 96:381-392, 1979) [13].
• The effects of isatin-beta-thiosemicarbazone on vaccinia virus-induced polypeptide synthesis has been examined by polyacrylamide gel electrophoresis and autoradiography [14].
• The p-cumate-degrading strain Pseudomonas putida F1 and the m- and p-toluate-degrading strain P. putida mt-2 transform indole-2-carboxylate and indole-3-carboxylate to colored products identified here as indigo, indirubin, and isatin [15].
• Similarly studies of the endogenous MAO inhibitor, tribulin, suggest that the output in panic disorder patients is similar to that of controls [16].
• In the present study, anticonvulsant activity of hydrazones, Schiff and Mannich bases of isatin were evaluated by maximal electroshock method (MES) and metrazol-induced convulsions (MET) at 30, 100 and 300 mg/kg dose levels [17].

Biological context of Isatin

• Both a temperature-sensitive mutant, Cts56, and an isatin-beta-thiosemicarbazone-dependent deletion mutant, G2A, in gene G2R have a characteristic and unique defect in late viral gene expression [18].
• The results show that the ts22 lesion and the action of isatin-beta-thiosemicarbazone may affect the same pathway, leading to the activation of latent 2-5A-dependent RNase and resulting in indiscriminate RNA degradation and inhibition of viral replication [19].
• However, the distribution of isatin binding sites in the brain is not known [20].
• Isatin, an endogenous monoamine oxidase inhibitor, triggers a dose- and time-dependent switch from apoptosis to necrosis in human neuroblastoma cells [21].
• Thus, in dopaminergic SH-SY5Y cells isatin induces cell death in dose- and time-dependent manner [21].

Anatomical context of Isatin

• 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 [22].
• Synthesis of vaccinia viral antigens in HeLa cells in the presence of isatin beta-thiosemicarbazone [23].
• In this study, several isatin analogues were tested as inhibitors of ANP-stimulated GC in rat brain and heart membranes [24].
• These observations suggest that the mechanism by which m-CPP elicits enhancing effects on urinary isatin excretion has something in common with stress response involving activation of hypothalamic CRF cells and the sympathetic nervous system [25].
• Survival of PMA-differentiated HL60 and FGF(2)-differentiated PC12 cells was not affected by 5-Hydroxyoxindole and isatin treatment, suggesting that endogenous oxindoles interact with growth factors signaling [26].

Associations of Isatin with other chemical compounds

• 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)) [27].
• Echinococcus multilocularis metacestodes: biochemical and ultrastructural investigations on the effect of isatin (2-3 indoline dione) in vivo [28].
• Starting from tryptamine 4 and isatin 5, a biomimetic approach to the pentacyclic substructure 1 of perophoramidine and communesin was developed [29].
• The rate of virus inactivation by N-methyl isatin beta-thiosemicarbazone is greatly enhanced and controlled by the addition of cupric sulphate [30].
• When treated with 0.1% isatin in absolute ethanol or acetone for 30 min and observed under violet-blue exciting light, eosinophil leucocyte granules show a bright green fluorescence [31].

Gene context of Isatin

• The effect of hANP was completely blocked by isatin, a potent antagonist of NPR (p < 0.01 vs. hANP) [32].
• Monoamine oxidase A-inhibiting components of urinary tribulin: purification and identification [33].
• 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) [34].
• 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) [34].
• Previous experiments with the antipoxviral drug isatin-beta-thiosemicarbazone suggest that lethal mutation of gene G2R would compensate for mutations in gene A18R [35].

Analytical, diagnostic and therapeutic context of Isatin

• This is the first study to demonstrate by HPLC that urinary isatin excretion is increased by stress [9].
• Isatin is anxiogenic in animal models at doses of 10-20 mg/kg and sedative at higher doses [36].
• A simple and one-pot protocol for the synthesis of indene-spiro-oxindole derivatives via TiCl4-mediated reaction between 1,1-diarylethylenes and isatin derivatives involving construction of two carbon-carbon bonds through tandem Prins and intramolecular Friedel-Crafts (PFC) reactions has been described [37].
• These observations suggest that isatin derivatives may have a role in the chemotherapy of infections caused by Echinococcus spp [28].
• Fluorimetric determination of isatin in human urine and serum by liquid chromatography postcolumn photoirradiation [38].

References