Effects of isatin, an endogenous MAO inhibitor, on acetylcholine and dopamine levels in the rat brain

Hamaue, Naoya; Terado, Mutsuko; Yamazaki, Noriko; Minami, Masaru; Endô, Tôru; Hirafuji, Masahiko; Monma, Yoshio; Togashi, Hiroko; Saito, Hideya

doi:10.1016/s0021-5198(19)40649-5

Cited by 3 publications

(6 citation statements)

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“… 32 Isatin is identified as a potent inhibitor for MAO, and its selectivity to MAO-B is more than that to MAO-A. 33 , 34…”

Section: Introductionmentioning

confidence: 99%

“…Glover et al, Clow et al, and Armando et al found that tribulin, an endogenous displacer benzodiazepine and monoamine oxidase inhibitor (MAO), has been detected in humans and rats (brain and heart). − The chemical composition of tribulin was unclear until Glower and colleagues discovered that isatin had features that are similar to endogenous tribulin . Isatin is identified as a potent inhibitor for MAO, and its selectivity to MAO-B is more than that to MAO-A. , …”

Section: Introductionmentioning

confidence: 99%

“…32 Isatin is identified as a potent inhibitor for MAO, and its selectivity to MAO-B is more than that to MAO-A. 33,34 MAOs are imperative enzymes that have been usually investigated for the treatment of neurological diseases such as Parkinson's disease (PD) and Alzheimer's disease (AD). The oxidative deamination of biogenic and xenobiotic amines is catalyzed by this enzyme, which changes their levels in the brain.…”

Section: ■ Introductionmentioning

confidence: 99%

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Exploration of the Detailed Structure–Activity Relationships of Isatin and Their Isomers As Monoamine Oxidase Inhibitors

2022

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Monoamine oxidase (MAO) is a protein with a key function in the catabolism of neuroamines in both central and peripheral parts of the body. MAO-A and -B are two isozymes of this enzyme which have emerged to be considered as a drug target for the treatment of neurodenerative disorders such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). Isatin is an endogenous small fragment, reversible inhibitor for MAO enzymes and is more selective for MAO-B than -A. Isatin is responsible for increasing the dopamine level in the brain by the inhibition of an MAO enzyme. The very few selective and reversible inhibitors existing for MAO proteins and the intensity of neurological diseases in humanity have opened a new door for researchers. Isatin has a polypharmacological profile in medicinal chemistry, is a reversible inhibitor for both the MAOs, and shows high selectivity potent inhibition for MAO-B. In this review, we discuss isatins and their analogues phthalide and phthalimide with structure–activity relationships (SARs), and this comprehensive information accelerates the ideas for design and development of a new class of MAO inhibitors for neurodegenerative diseases.

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“… 32 Isatin is identified as a potent inhibitor for MAO, and its selectivity to MAO-B is more than that to MAO-A. 33 , 34…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: ■ Introductionmentioning

confidence: 99%

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Exploration of the Detailed Structure–Activity Relationships of Isatin and Their Isomers As Monoamine Oxidase Inhibitors

2022

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“…Isatin has been extensively studied in behavioral and metabolic assays, and >90 proteins have been identified through proteomic analysis as its potential biological targets . It acts as a potent inhibitor of human mitochondrial monoamine oxidase B (MAO-B) and administered exogenously was found to significantly increase the levels of acetylcholine, choline, and dopamine in rat brain tissues . It is a flexible and versatile synthetic scaffold, consisting of an indole nucleus and two types of carbonyl groups, a keto and a lactam group that render it a favorable building block for Schiff base reactions, heterocyclic compound synthetic strategies, and pharmacophore development …”

Section: Introductionmentioning

confidence: 99%

“…8 It acts as a potent inhibitor of human mitochondrial monoamine oxidase B (MAO-B) 9 and administered exogenously was found to significantly increase the levels of acetylcholine, choline, and dopamine in rat brain tissues. 10 It is a flexible and versatile synthetic scaffold, consisting of an indole nucleus and two types of carbonyl groups, a keto and a lactam group that render it a favorable building block for Schiff base reactions, heterocyclic compound synthetic strategies, and pharmacophore development. 11 Isatin derivatives possess a wide range of biological activities, including antimicrobial, anti-HIV, antiviral, antimalarial, anticancer, anticonvulsant, antiasthmatic, anti-inflammatory, and analgesic activities.…”

Section: ■ Introductionmentioning

confidence: 99%

Novel Isatin Thiosemicarbazone Derivatives as Potent Inhibitors of β-Amyloid Peptide Aggregation and Toxicity

Sagnou

Mavroidi

Kaminari

et al. 2020

ACS Chem. Neurosci.

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Inhibition of β-amyloid peptide (Αβ) aggregation in Alzheimer’s disease (AD) is among the therapeutic approaches against AD which still attracts scientific research interest. In the search for compounds that interact with Aβ and disrupt its typical aggregation course toward oligomeric or polymeric toxic assemblies, small organic molecules of natural origin, combining low molecular weight (necessary blood-brain barrier penetration) and low toxicity (necessary for pharmacological application), are greatly sought after. Isatin (1H-indoline-2,3-dione), a natural endogenous indole, and many of its derivatives exhibit a wide spectrum of neuropharmacological and chemotherapeutic properties. The synthesis and biological evaluation of four new isatins as inhibitors of Aβ aggregation is presented herein. In these derivatives, the N-phenyl thiosemicarbazide moiety is joined at the 3-oxo position of isatin through Schiff base formation, and substitutions are present at the indole nitrogen and position 5 of the isatin core. Biophysical studies employing circular dichroism, thioflavin T fluorescence assay, and transmission electron microscopy reveal the potential of the isatin thiosemicarbazones (ITSCs) to alter the course of Αβ aggregation, with two of the derivatives exhibiting outstanding inhibition of the aggregation process, preventing completely the formation of amyloid fibrils. Furthermore, in in vitro studies in primary neuronal cell cultures, the ITSCs were found to inhibit the Aβ-induced neurotoxicity and reactive oxygen species production at concentrations as low as 1 μM. Taken all together, the novel ITSCs can be considered as privileged structures for further development as potential AD therapeutics.

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The evaluation of isatin analogues as inhibitors of monoamine oxidase

et al. 2023

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The small molecule, isatin, is a well‐known reversible inhibitor of the monoamine oxidase (MAO) enzymes with IC50 values of 12.3 and 4.86 μM for MAO‐A and MAO‐B, respectively. While the interaction of isatin with MAO‐B has been characterized, only a few studies have explored structure–activity relationships (SARs) of MAO inhibition by isatin analogues. The current study therefore evaluated a series of 14 isatin analogues as in vitro inhibitors of human MAO‐A and MAO‐B. The results indicated good potency MAO inhibition for some isatin analogues with five compounds exhibiting IC50 < 1 μM. 4‐Chloroisatin (1b) and 5‐bromoisatin (1f) were the most potent inhibitors with IC50 values of 0.812 and 0.125 μM for MAO‐A and MAO‐B, respectively. These compounds were also found to be competitive inhibitors of MAO‐A and MAO‐B with Ki values of 0.311 and 0.033 μM, respectively. Among the SARs, it was interesting to note that C5‐substitution was particularly beneficial for MAO‐B inhibition. MAO inhibitors are established drugs for the treatment of neuropsychiatric and neurodegenerative disorders, while potential new roles in prostate cancer and cardiovascular disease are being investigated.

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Effects of isatin, an endogenous MAO inhibitor, on acetylcholine and dopamine levels in the rat brain

Cited by 3 publications

References 0 publications

Exploration of the Detailed Structure–Activity Relationships of Isatin and Their Isomers As Monoamine Oxidase Inhibitors

Exploration of the Detailed Structure–Activity Relationships of Isatin and Their Isomers As Monoamine Oxidase Inhibitors

Novel Isatin Thiosemicarbazone Derivatives as Potent Inhibitors of β-Amyloid Peptide Aggregation and Toxicity

The evaluation of isatin analogues as inhibitors of monoamine oxidase

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