Disease relevance of Oxindol

• Oxindole in pathogenesis of hepatic encephalopathy [1].
• To study the role that oxindole plays in the neurological symptoms associated with acute liver failure, we measured the changes of its concentration in the brain after massive liver damage, and we investigated the possible metabolic pathways leading to its synthesis [2].
• Rats treated with oxindole (10-100 mg/kg i.p.), a putative tryptophan metabolite, showed decreased spontaneous locomotor activity, loss of the righting reflex, hypotension, and reversible coma [2].
• The biosynthetic pigment from Chromobacterium violaceum BB-78, 1,3-dihydro-2H-indol-2-one and its derivatives exhibit biological activities such as antimicrobial action, low hemolytic effects on red blood cells and in vitro trypanocide activity [3].
• A novel oxindole was discovered as an HIV non-nucleoside reverse transcriptase inhibitor via HTS using a cell-based assay [4].

High impact information on Oxindol

• Cocrystallographic studies of SU6668 in the catalytic domain of FGF receptor 1 substantiated the adenine mimetic properties of its oxindole core [5].
• The antiangiogenic drugs included (Z)-3-[4-(dimethylamino)benzylidenyl]indolin-2-one (a platelet-derived growth factor receptor beta and a fibroblast growth factor receptor 1 kinase inhibitor) and oxindole (a vascular endothelial growth factor receptor 2 kinase inhibitor) [6].
• The 3-substituted 2-oxindole tenidap has proven anti-inflammatory actions both in vivo and in vitro, among which is the inhibition of TNF and IL-1 production by monocytes following activation by LPS [7].
• The synthesis revolves around the Li[Me(3)AlSPh]-promoted isomerization of iminobenzoxazine 33 to quinazolinone 34, an N-acyliminium ion cyclization that converts enamide 9 to bridged indole 35, and rearrangement of 35 to oxindole ent-6 [8].
• We show the oxindole inhibitor GW297361 elicits a Pho85-selective response in cells despite having a 20-fold greater biochemical potency for Cdk1 in vitro [9].

Chemical compound and disease context of Oxindol

• Studies on the pharmacological properties of oxindole (2-hydroxyindole) and 5-hydroxyindole: are they involved in hepatic encephalopathy [10]?
• In this study, we tested 3 inhibitors of CDK4, 3-aminothioacridone (3-ATA), thioacridone (TA), and oxindole, for their effects on DNA synthesis and viability in primary T-ALL [11].

Biological context of Oxindol

• We previously described the inhibitory activity of the 2-indolinone derivative RPI-1 (formerly Cpdl) on the tyrosine kinase activity and transforming ability of the products of the RET/PTC1 oncogene exogenously expressed in murine cells [12].
• 4. Oxindole (0.3-3 mM) increased the threshold and the latency of firing action potentials elicited by depolarizing steps without changing the duration or the peak amplitude of the spikes [13].
• Reduction of the nitro group followed by intramolecular amination with ketone and aldehyde and amidation with ester produced indoline and oxindole derivatives, respectively, in excellent yield [14].
• Hydroxylation in several positions on both the oxindole and thienyl rings of tenidap represents the major routes of metabolism; most of these metabolites are subsequently conjugated [15].
• Oxindole alkaloids from Uncaria tomentosa induce apoptosis in proliferating, G0/G1-arrested and bcl-2-expressing acute lymphoblastic leukaemia cells [16].

Anatomical context of Oxindol

• In intracellular recordings, oxindole (0.1-3 mM) did not affect the resting membrane potential or the neuronal input resistance, but reduced the probability of firing action potentials upon either synaptic or direct activation of the pyramidal cells [13].
• Tetracyclic oxindole alkaloids dose-dependently reduce the activity of pentacyclic oxindole alkaloids on human endothelial cells [17].
• Here, we investigated for the first time the antiproliferative and apoptotic effects of highly purified oxindole alkaloids, namely isopteropodine (A1), pteropodine (A2), isomitraphylline (A3), uncarine F (A4) and mitraphylline (A5) obtained from Uncaria tomentosa, a South American Rubiaceae, on human lymphoblastic leukaemia T cells (CCRF-CEM-C7H2) [16].
• Tetracyclic oxindole alkaloids act on the central nervous system, whereas pentacyclic oxindole alkaloids affect the cellular immune system [18].
• Methanol extracts of Hamelia patens containing oxindole alkaloids relax KCl-induced contraction in rat myometrium [19].

Associations of Oxindol with other chemical compounds

• In this study, novel synthetic arylidene 2-indolinone compounds were evaluated as inhibitors of the ret/ptc1 tyrosine kinase [20].
• Oral administration of neomycin, a broad-spectrum, locally acting antibiotic agent able to reduce intestinal flora, significantly decreased brain oxindole content [2].
• Two closely related classes of oxindole-based compounds, 1H-indole-2,3-dione 3-phenylhydrazones and 3-(anilinomethylene)-1,3-dihydro-2H-indol-2-ones, were shown to potently inhibit cyclin-dependent kinase 2 (CDK2) [21].
• Extension of this transformation from carboxylate nucleophiles to carbon analogues such as allylsilane, silyl enol ether, and silyl ketene iminal bearing substrates led to the formation of spirocyclic oxindole derivatives in good yields with complete regioselectivity for C(3) cyclization and with good diastereoselectivity where relevant [22].
• Of interest was the fact that the reaction of N-(tert-butoxycarbonyl)-L-tryptophan with H2O2/horseradish peroxidase mainly afforded the same oxindole- and formylkynurenine-type products as those obtained in the hypoxanthine/xanthine oxidase/Fe(III)-EDTA system [23].

Gene context of Oxindol

• Remarkable product preferences between the desaturation pathway to form the methyleneindolenine by CYP2F1 and the ring epoxidation pathway to form the oxindole by CYP1A2, were observed [24].
• Oxindole-based compounds are selective inhibitors of Plasmodium falciparum cyclin dependent protein kinases [25].
• We previously reported that novel oxindole derivatives have been identified as GHS-R agonists from our internal chemical library [26].
• These results indicate that isorhynchophylline and isocorynoxeine preferentially suppress 5-HT2A receptor function in the brain probably via a competitive antagonism at 5-HT2A receptor sites and that the configuration of the oxindole moiety of isorhynchophylline is essential for their antagonistic activity at the 5-HT2A receptor [27].
• METHODS: We investigated the cellular effects of RPI-1, a novel 2-indolinone Ret tyrosine kinase inhibitor on cells that express RET C634 oncogenic mutants common in the MEN2A syndrome: NIH3T3 fibroblasts transfected with RET(C634R) and human medullary thyroid carcinoma TT cells that express endogenous RET(C634W) [28].

Analytical, diagnostic and therapeutic context of Oxindol

• Three-dimensional HPLC analysis indicated that the water extract of this herb contains several different chemical compounds, including oxindole and indol alkaloids, which have been regarded as neuroprotective [29].
• The metabolite was isolated by thin-layer chromatography and determined to be 1,3-dihydro-2H-indol-2one (oxindole) by UV spectroscopy (lambdaMAX, 247 nm) and mass spectrometry (m/z, 133) [30].
• Improved method for the determination of oxindole alkaloids in Uncaria tomentosa by high performance liquid chromatography [31].
• Isorhynchophylline is a major oxindole alkaloid found in Uncaria species which have long been used in traditional Chinese medicine [27].
• Monoterpenoid oxindole alkaloid production by Uncaria tomentosa (Willd) D.C. cell suspension cultures in a stirred tank bioreactor [32].

References