scholarly journals Aporphine Alkaloids from Guatteria stenopetala (Annonaceae)

2008 ◽  
Vol 3 (4) ◽  
pp. 1934578X0800300 ◽  
Author(s):  
María Rodríguez ◽  
Elsy Bastidas ◽  
Mildred Rodríguez ◽  
Edgar Lucena ◽  
Anibal Castillo ◽  
...  
Keyword(s):  
Monoamine Oxidase ◽  
Mao Inhibitors ◽  
Isoquinoline Alkaloids ◽  
Inhibitory Effects ◽  
Mao B ◽  
Parkinson’S Diseases

Guatteria species (Annonaceae) are rich in isoquinoline alkaloids that contain a restricted β-phenethylamine moiety and thus have potential as monoamine oxidase (MAO) inhibitors for the treatment of Alzheimer's and Parkinson's diseases. Three aporphine alkaloids have been isolated from G. stenopetala, the known oxoaporphine dicentrinone (1), and two novel compounds, N-methyldicentrinone (2) and 4,5-dioxodehydrodicentrine (3). Their inhibitory effects on MAO-B were evaluated, but none of them was significantly active.

scholarly journals Quercetin and Related Chromenone Derivatives as Monoamine Oxidase Inhibitors: Targeting Neurological and Mental Disorders

Molecules ◽  
2019 ◽  
Vol 24 (3) ◽  
pp. 418 ◽  
Author(s):  
Priyanka Dhiman ◽  
Neelam Malik ◽  
Eduardo Sobarzo-Sánchez ◽  
Eugenio Uriarte ◽  
Anurag Khatkar
Keyword(s):  
Monoamine Oxidase ◽  
Neurodegenerative Disorders ◽  
Research Groups ◽  
Mao B ◽  
Chemistry Research ◽  
Current Review ◽  
Treatment Of Depression ◽  
New Findings ◽  
Parkinson’S Diseases ◽  
Preclinical Trials

Monoamine oxidase inhibitions are considered as important targets for the treatment of depression, anxiety, and neurodegenerative disorders, including Alzheimer’s and Parkinson’s diseases. This has encouraged many medicinal chemistry research groups for the development of most promising selective monoamine oxidase (MAO) inhibitors. A large number of plant isolates also reported for significant MAO inhibition potential in recent years. Differently substituted flavonoids have been prepared and investigated as MAO-A and MAO-B inhibitors. Flavonoid scaffold showed notable antidepressant and neuroprotective properties as revealed by various and established preclinical trials. The current review made an attempt to summarizing and critically evaluating the new findings on the quercetin and related flavonoid derivatives functions as potent MAO isoform inhibitors.

human monoamine oxidase (hMAO) A and hMAO B inhibitors from Artemisia dracunculus L. herniarin and skimmin: human mononamine oxidase A and B inhibitors from A. dracunculus L.

2020 ◽  
Vol 75 (11-12) ◽  
pp. 459-466
Author(s):  
Tuba Aydin ◽  
Hulya Akincioglu ◽  
Mehmet Gumustas ◽  
Ilhami Gulcin ◽  
Cavit Kazaz ◽  
...  
Keyword(s):  
Monoamine Oxidase ◽  
High Performance ◽  
2D Nmr ◽  
Inhibitory Effects ◽  
Artemisia Dracunculus ◽  
Mao B ◽  
H Nmr ◽  
Mao A ◽  
Pure Compounds ◽  
Nmr Methods

AbstractThe aim of this study was to investigate the effects of extracts and pure Artemisia dracunculus L. (tarragon) metabolites on the antimonoamine oxidase and anticholinesterase activities. The compounds were characterized as stigmasterol (1), herniarin (2), (2E,4E)-1-(piperidin-1-yl)undeca-2,4-diene-8,10-diyn-1-one (3), (2E,4E)-N-isobutylundeca-2,4-dien-8,10-diynamide (4), 3,4-dehydroherniarin (5) and skimmin (6) by 1H-NMR, 13C-NMR, 1D and 2D NMR methods. The compounds 5 and 6 were isolated from tarragon for the first time. The extracts and pure compounds have inhibitory effects on the human monoamine oxidase (hMAO) A and B enzymes, whereas they did not exhibit any anticholinesterase activities. Among the tarragon compounds, only 2 and 6 compounds showed the inhibitory effects against hMAO A (IC50 = 51.76 and 73.47 μM, respectively) and hMAO B (IC50 = 0.84 and 1.63 mM, respectively). In the study, herniarin content in the extracts was also analysed by high-performance liquid chromatography and it was found that there was a relationship between the inhibition effects of the extracts and their herniarin content.

Developing a Multi-target Model to Predict the Activity of Monoamine Oxidase A and B Drugs

2020 ◽  
Vol 20 (18) ◽  
pp. 1593-1600 ◽  
Author(s):  
Riccardo Concu ◽  
Michael González-Durruthy ◽  
Maria Natália D.S. Cordeiro
Keyword(s):  
Side Effects ◽  
Monoamine Oxidase ◽  
Statistical Tests ◽  
Qsar Model ◽  
Monoamine Oxidase A ◽  
Mao Inhibitors ◽  
Computational Approaches ◽  
Linear Discriminant ◽  
Mao B ◽  
Mao A

Introduction: Monoamine oxidase inhibitors (MAOIs) are compounds largely used in the treatment of Parkinson’s disease (PD), Alzheimer’s disease and other neuropsychiatric disorders since they are closely related to the MAO enzymes activity. The two isoforms of the MAO enzymes, MAO-A and MAO-B, are responsible for the degradation of monoamine neurotransmitters and due to this, relevant efforts have been devoted to finding new compounds with more selectivity and less side effects. One of the most used approaches is based on the use of computational approaches since they are time and money-saving and may allow us to find a more relevant structure-activity relationship. Objectives: In this manuscript, we will review the most relevant computational approaches aimed at the prediction and development of new MAO inhibitors. Subsequently, we will also introduce a new multitask model aimed at predicting MAO-A and MAO-B inhibitors. Methods: The QSAR multi-task model herein developed was based on the use of the linear discriminant analysis. This model was developed gathering 5,759 compounds from the public dataset Chembl. The molecular descriptors used was calculated using the Dragon software. Classical statistical tests were performed to check the validity and robustness of the model. Results: The herein proposed model is able to correctly classify all the 5,759 compounds. All the statistical performed tests indicated that this model is robust and reproducible. Conclusion: MAOIs are compounds of large interest since they are largely used in the treatment of very serious illness. These inhibitors may lose efficacy and produce severe side effects. Due to this, the development of selective MAO-A or MAO-B inhibitors is crucial for the treatment of these diseases and their effects. The herein proposed multi-target QSAR model may be a relevant tool in the development of new and more selective MAO inhibitors.

Thyroid iodide transport is reduced by administration of monoamine oxidase A inhibitors to rats

1994 ◽  
Vol 143 (2) ◽  
pp. 303-308 ◽  
Author(s):  
A M Cabanillas ◽  
A M Masini-Repiso ◽  
M E Costamagna ◽  
C Pellizas ◽  
A H Coleoni
Keyword(s):  
Monoamine Oxidase ◽  
Transport Mechanism ◽  
Monoamine Oxidase A ◽  
Mao Inhibitors ◽  
Iodide Uptake ◽  
Mao B ◽  
Iodide Transport ◽  
Mao A ◽  
Mao Activity

Abstract The present work was addressed to study a possible relationship between monoamine oxidase (MAO) and the thyroid iodide transport mechanism. Normal rats treated with clorgyline (a selective MAO-A inhibitor) or tranylcypromine (a non-selective MAO inhibitor) showed a significantly diminished thyroid MAO activity, while deprenyl and pargyline (MAO-B inhibitors) did not modify the thyroidal enzyme activity with respect to the control group. Under these conditions, in vivo iodide transport was reduced both by clorgyline and tranylcypromine administration whereas it remained unchanged after treatment with MAO-B inhibitors. The effect of MAO inhibitors on thyroid MAO activity and in vivo iodide transport was also evaluated in rats treated with exogenous thyrotrophin (TSH) after endogenous TSH secretion blockade produced by T4 administration. In this condition, thyroid MAO activity was significantly lowered by clorgyline and was not modified by deprenyl. In contrast to the results observed in normal rats, in vivo iodide transport in TSH-treated rats remained unaltered after treatment either with clorgyline or deprenyl. MAO activity evaluated in bovine thyroid follicles in primary culture was highly sensitive to low concentrations of clorgyline (<10 nmol/l) and relatively insensitive to deprenyl, a finding that indicates a predominance of the MAO-A isoform in the follicular cells in culture. When clorgyline (0·1 and 1 μmol/l) or deprenyl (1 μmol/l) were added to the culture medium, no modifications in the active transport of iodide were observed. These results indicate the absence of a direct linkage between thyroid MAO activity and the active iodide transport. MAO inhibitors (particularly MAO-A inhibitors) do not appear to be responsible for an in vivo diminished thyroid iodide uptake through a direct action on the iodide transport mechanism. An indirect effect of MAO-A inhibitors on thyroid iodide transport mediated by the accumulation of monoamines in neuroendocrine areas involved in TSH regulation is suggested. Journal of Endocrinology (1994) 143, 303–308

scholarly journals Inhibition of Butyrylcholinesterase and Human Monoamine Oxidase-B by the Coumarin Glycyrol and Liquiritigenin Isolated from Glycyrrhiza uralensis

Molecules ◽  
2020 ◽  
Vol 25 (17) ◽  
pp. 3896
Author(s):  
Geum Seok Jeong ◽  
Myung-Gyun Kang ◽  
Joon Yeop Lee ◽  
Sang Ryong Lee ◽  
Daeui Park ◽  
...  
Keyword(s):  
Monoamine Oxidase ◽  
Binding Affinity ◽  
Competitive Inhibitor ◽  
Glycyrrhiza Uralensis ◽  
Form Hydrogen Bond ◽  
Docking Simulations ◽  
Mao B ◽  
Mao A ◽  
Ic50 Values ◽  
Noncompetitive Inhibitor

Eight compounds were isolated from the roots of Glycyrrhiza uralensis and tested for cholinesterase (ChE) and monoamine oxidase (MAO) inhibitory activities. The coumarin glycyrol (GC) effectively inhibited butyrylcholinesterase (BChE) and acetylcholinesterase (AChE) with IC50 values of 7.22 and 14.77 µM, respectively, and also moderately inhibited MAO-B (29.48 µM). Six of the other seven compounds only weakly inhibited AChE and BChE, whereas liquiritin apioside moderately inhibited AChE (IC50 = 36.68 µM). Liquiritigenin (LG) potently inhibited MAO-B (IC50 = 0.098 µM) and MAO-A (IC50 = 0.27 µM), and liquiritin, a glycoside of LG, weakly inhibited MAO-B (>40 µM). GC was a reversible, noncompetitive inhibitor of BChE with a Ki value of 4.47 µM, and LG was a reversible competitive inhibitor of MAO-B with a Ki value of 0.024 µM. Docking simulations showed that the binding affinity of GC for BChE (−7.8 kcal/mol) was greater than its affinity for AChE (−7.1 kcal/mol), and suggested that GC interacted with BChE at Thr284 and Val288 by hydrogen bonds (distances: 2.42 and 1.92 Å, respectively) beyond the ligand binding site of BChE, but that GC did not form hydrogen bond with AChE. The binding affinity of LG for MAO-B (−8.8 kcal/mol) was greater than its affinity for MAO-A (−7.9 kcal/mol). These findings suggest GC and LG should be considered promising compounds for the treatment of Alzheimer’s disease with multi-targeting activities.

Development of Monoamine Oxidase and Aldehyde Dehydrogenase in Reaggregating Cultures of Fetal Rat Brain Cells

1989 ◽  
Vol 16 (3) ◽  
pp. 281-286
Author(s):  
Olof Tottmar ◽  
Maria Söderbäck ◽  
Anders Aspberg
Keyword(s):  
Monoamine Oxidase ◽  
Rat Brain ◽  
Aldehyde Dehydrogenase ◽  
Brain Cells ◽  
Mao B ◽  
Adult Rat ◽  
Fetal Rat ◽  
Adult Rat Brain ◽  
Mao A ◽  
Fetal Rat Brain

The development of monoamine oxidase (MAO) and aldehyde dehydrogenase (ALDH) in reaggregation cultures of fetal rat brain cells was compared with that of enzymatic markers for glial and neuronal cells. Only MAO-A was detected in the cultures during the first week, but, during the following three weeks, the activity of MAO-B increased more rapidly than that of MAO-A. The ratio MAO-A/MAO-B in four-week aggregates was close to that found in the adult rat brain. The activity of ALDH started to increase rapidly after 15 days, and the developmental pattern was intermediate to those of the glial and neuronal markers. The activity after four weeks was close to that found in the adult rat brain. Epidermal growth factor (EGF) caused a slight decrease in the activities of the low-Km ALDH (after four weeks) and the neuronal marker, choline acetyltransferase (after two weeks), whereas the other markers were not affected. By contrast, the activities of MAO-A and MAO-B were greatly increased during almost the entire culture period. It is suggested that this effect of EGF was the result of increased mitotic activity and/or biochemical differentiation of other cell types present in the cell aggregates, e.g. capillary endothelial cells.

scholarly journals 4-Phenethyl-1-Propargylpiperidine-Derived Dual Inhibitors of Butyrylcholinesterase and Monoamine Oxidase B

Molecules ◽  
2021 ◽  
Vol 26 (14) ◽  
pp. 4118
Author(s):  
Tjaša Mazej ◽  
Damijan Knez ◽  
Anže Meden ◽  
Stanislav Gobec ◽  
Matej Sova
Keyword(s):  
Monoamine Oxidase ◽  
Docking Studies ◽  
Monoamine Oxidase B ◽  
Mao B ◽  
Initial Expectation ◽  
Excellent Starting Point ◽  
Starting Point ◽  
Dependent Inhibition ◽  
Dual Inhibitors ◽  
Time Dependent Inhibition

The multi-target-directed ligands (MTDLs) strategy is encouraged for the development of novel modulators targeting multiple pathways in the neurodegenerative cascade typical for Alzheimer’s disease (AD). Based on the structure of an in-house irreversible monoamine oxidase B (MAO-B) inhibitor, we aimed to introduce a carbamate moiety on the aromatic ring to impart cholinesterase (ChE) inhibition, and to furnish multifunctional ligands targeting two enzymes that are intricately involved in AD pathobiology. In this study, we synthesized three dual hMAO-B/hBChE inhibitors 13–15, with compound 15 exhibiting balanced, low micromolar inhibition of hMAO-B (IC50 of 4.3 µM) and hBChE (IC50 of 8.5 µM). The docking studies and time-dependent inhibition of hBChE confirmed the initial expectation that the introduced carbamate moiety is responsible for covalent inhibition. Therefore, dual-acting compound 15 represents an excellent starting point for further optimization of balanced MTDLs.

scholarly journals Positive Modulation of PinkNelumbo nuciferaFlowers on Memory Impairment, Brain Damage, and Biochemical Profiles in Restraint Rats

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Thawatchai Prabsattroo ◽  
Jintanaporn Wattanathorn ◽  
Pichet Somsapt ◽  
Opass Sritragool
Keyword(s):  
Oxidative Stress ◽  
Monoamine Oxidase ◽  
Spatial Memory ◽  
Brain Damage ◽  
Memory Deficit ◽  
Ki67 Expression ◽  
Mao B ◽  
Serum Corticosterone ◽  
Neuron Density ◽  
Oxidative Stress Status

Due to the crucial role of oxidative stress in the stress-induced memory deficit, the benefit of substance possessing antioxidant effect is focused. Since no data are available, we aimed to determine the effect ofNelumbo nuciferaflowers extract on spatial memory and hippocampal damage in stressed rats. Male Wistar rats, weighing 250–350 g, were orally givenN. nuciferaextract at doses of 10, 10, and 200 mg·kg−145 minutes before the exposure to 12-hour restraint stress. The spatial memory and serum corticosterone were assessed at 7 and 14 days of study period. At the end of study, acetylcholinesterase (AChE), monoamine oxidase type A and monoamine oxidase type B (MAO-A and MAO-B), oxidative stress status, neuron density, and Ki67 expression in hippocampus were also assessed. The results showed thatN. nuciferaextract decreased memory deficit and brain damage, serum corticosterone, oxidative stress status, AChE, and MAO-A and MAO-B activities but increased neuron density and Ki67 expression in hippocampus. These suggested that the improved oxidative stress status, adult neurogenesis, and cholinergic and monoaminergic functions might be responsible for the protective effect against stress-related brain damage and dysfunction of the extract. Therefore,N. nuciferaextract is the potential neuroprotective and memory enhancing agent. However, further researches are still required.

scholarly journals In Vitro,In Vivo, and Clinical Studies of Tedizolid To Assess the Potential for Peripheral or Central Monoamine Oxidase Interactions

2013 ◽  
Vol 57 (7) ◽  
pp. 3060-3066 ◽  
Author(s):  
S. Flanagan ◽  
K. Bartizal ◽  
S. L. Minassian ◽  
E. Fang ◽  
P. Prokocimer
Keyword(s):  
Blood Pressure ◽  
Monoamine Oxidase ◽  
Clinical Research ◽  
Systolic Blood Pressure ◽  
Clinical Studies ◽  
Geometric Mean ◽  
Interaction Study ◽  
Mao B ◽  
Mao A

ABSTRACTTedizolid phosphate is a novel oxazolidinone prodrug whose active moiety, tedizolid, has improved potency against Gram-positive pathogens and pharmacokinetics, allowing once-daily administration. Given linezolid warnings for drug-drug and drug-food interactions mediated by monoamine oxidase (MAO) inhibition, including sporadic serotonergic toxicity, these studies evaluated tedizolid for potential MAO interactions.In vitro, tedizolid and linezolid were reversible inhibitors of human MAO-A and MAO-B; the 50% inhibitory concentration (IC50) for tedizolid was 8.7 μM for MAO-A and 5.7 μM for MAO-B and 46.0 and 2.1 μM, respectively, with linezolid. Tedizolid phosphate was negative in the mouse head twitch model of serotonergic activity. Two randomized placebo-controlled crossover clinical studies assessed the potential of 200 mg/day tedizolid phosphate (at steady state) to enhance pressor responses to coadministered oral tyramine or pseudoephedrine. Sensitivity to tyramine was determined by comparing the concentration of tyramine required to elicit a ≥30-mmHg increase in systolic blood pressure (TYR30) when administered with placebo versus tedizolid phosphate. The geometric mean tyramine sensitivity ratio (placebo TYR30/tedizolid phosphate TYR30) was 1.33; a ratio of ≥2 is considered clinically relevant. In the pseudoephedrine study, mean maximum systolic blood pressure was not significantly different when pseudoephedrine was coadministered with tedizolid phosphate versus placebo. In summary, tedizolid is a weak, reversible inhibitor of MAO-A and MAO-Bin vitro. Provocative testing in humans and animal models failed to uncover significant signals that would suggest potential for hypertensive or serotonergic adverse consequences at the therapeutic dose of tedizolid phosphate. Clinical studies are registered atwww.clinicaltrials.govas NCT01539473 (tyramine interaction study conducted at Covance Clinical Research Center, Evansville, IN) and NCT01577459 (pseudoephedrine interaction study conducted at Vince and Associates Clinical Research, Overland Park, KS).

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