Isatin is an endogenous oxidized indole that influences a range of processes in vivo and in vitro. It has a distinct and discontinuous distribution in the brain and [3H]isatin binding sites are widely distributed in rat brain sections. The highest labelling is found in hypothalamic nuclei and in the cortex, hippocampus, and cerebellum (Crumeyrolle-Arias et al., 2003). However, the properties of most isatin binding sites and their physiological ligands remain unknown. In the present study the effects of three endogenous oxidized indoles (oxindole, 5-hyxdoxyoxindole, and isatin) on [3H]isatin binding were investigated in rat brain sections. In most regions cold isatin (0.2 mM) significantly reduced [3H]isatin binding. In addition to isatin, the other endogenous oxidized indoles, 5-hydroxyoxindole and oxindole were effective in displacing [3H]isatin. Total irreversible inhibition of monoamine oxidases caused inhibition of specific [3H]isatin binding in 7 of 10 brain region studied. This was accompanied by altered sensitivity of [3H]isatin binding to these indoles, including regions where a decrease of specific binding was not detected. The combinations of the three oxidized indoles produced two clear effects: augmentation (potentiation) and attenuation (blockade) of inhibitory activity compared with the independent effects of these compounds. The different effects of oxidized indoles and their combinations (isatin + 5-hydroxyoxindole and isatin + oxindole) in various brain regions therefore suggest an interaction of [(3H]isatin with different and multiple isatin-binding sites, which exhibit different sensitivity to endogenous oxidizing indoles.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1007/978-3-211-73574-9_4 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Multicomponent reaction for synthesis, molecular docking, and anti-inflammatory evaluation of novel indole-thiazole hybrid derivatives.
Mol Divers
August 2024
Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, 62511, Egypt.
In this article, novel thiazol-indolin-2-one derivatives 4a-f have been synthesized via treatment of thiosemicarbazide (1) with some isatin derivative 2a-f and N-(4-(2-bromoacetyl)phenyl)-4-tolyl-sulfonamide (3) under reflux in ethanol in the presence of triethyl amine (TEA). The structures of new products were elucidated by elemental and spectral analyses. Moreover, all compounds were investigated for their in vivo anti-inflammatory activity using celecoxib as a reference drug.
View Article and Find Full Text PDFDiscovery and prospects of new heterocyclic Isatin-hydrazide derivative with a novel role as estrogen receptor α degrader in breast cancer cells.
Front Chem
July 2024
Department of Life Sciences, Syed Babar Ali School of Science and Engineering, Lahore University of Management Sciences (LUMS), Lahore, Pakistan.
Isatin, a heterocycle scaffold, is the backbone of many anticancer drugs and has previously been reported to engage multiple cellular targets and mechanisms, including angiogenesis, cell cycle, checkpoint pathways and multiple kinases. Here, we report that a novel isatin derivative, 5i, degrades estrogen receptor alpha (ERα) in estrogen-dependent breast cancer cells. This effect of the isatin nucleus has not been previously reported.
View Article and Find Full Text PDFDesign, Synthesis of Novel 1,2,3-Triazole Pendent Quinazolinones and Their Cytotoxicity against MCF-7 Cell Line.
Chem Biodivers
December 2023
Department of Chemistry, University College of Science, Osmania University, Hyderabad, 500007, Telangana, India.
A library of 6-(((1-(substitutedphenyl)-1H-1,2,3-triazol-4-yl)methyl) amino)-3-methylquinazolin-4(3H)-one analogues synthesized from Isatin precursor through a series of nitration, reduction, hydrolysis, cyclization and click reaction. The structures of compounds were characterized by spectral data including IR, H-NMR, C NMR and Mass. The novel quinazolinone - 1,2,3-triazoles were screened for their cytotoxicity against the human breast adenocarcinoma cell lines MCF-7 by MTT assay.
View Article and Find Full Text PDFNew 6'-Amino-5'-cyano-2-oxo-1,2-dihydro-1'-spiro[indole-3,4'-pyridine]-3'-carboxamides: Synthesis, Reactions, Molecular Docking Studies and Biological Activity.
Molecules
April 2023
Department of Chemistry, North Caucasus Federal University, 1a Pushkin St., 355017 Stavropol, Russia.
The purpose of this work was to prepare new isatin- and monothiomalondiamide-based indole derivatives, as well as to study the properties of the new compounds. The four-component reaction of 5-R-isatins (R = H, CH), malononitrile, monothiomalonamide (3-amino-3-thioxo- propanamide) and triethylamine in hot EtOH yields a mixture of isomeric triethylammonium 6'-amino-3'-(aminocarbonyl)-5'-cyano-2-oxo-1,2-dihydro-1'- and 6'-amino-3'-(aminocarbonyl)- 5'-cyano-2-oxo-1,2-dihydro-3'-spiro[indole-3,4'-pyridine]-2'-thiolates. The reactivity and structure of the products was studied.
View Article and Find Full Text PDFSynthesis and biological evaluation of isatin derivatives containing 1,3,4-thiadiazole as potent a-glucosidase inhibitors.
Bioorg Med Chem Lett
December 2021
School of Chemistry and Chemical Engineering, Hunan University of Science and Technology, Xiangtan 411201, China. Electronic address:
A series of (Z)-3-(2-(1,3,4-thiadiazol-2-yl)hydrazono)-1-substituted indolin-2-ones derivatives (3a-3m) were designed and synthesized. All newly synthesized compounds were evaluated for their a-glucosidase inhibitory activity with resveratrol as positive control in vitro. Except for 3i and 3j, all of the compounds showed a potent inhibitory activity against a-glucosidase with IC values in the range of 3.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!