scholarly journals Design, synthesis, molecular modelling and in vitro screening of monoamine oxidase inhibitory activities of novel quinazolyl hydrazine derivatives

2020 ◽  
Vol 7 (4) ◽  
pp. 200050
Author(s):  
Adel Amer ◽  
Abdelrahman H. Hegazi ◽  
Mohammed Khalil Alshekh ◽  
Hany E. A. Ahmed ◽  
Saied M. Soliman ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Monoamine Oxidase ◽  
In Vitro Screening ◽  
Phenyl Substituent ◽  
Design Synthesis ◽  
Mao B ◽  
Mao A ◽  
Ft Ir ◽  
Inhibitory Activities

A new series of N'-substituted benzylidene-2-(4-oxo-2-phenyl-1,4-dihydroquinazolin-3(2H)-yl)acetohydrazide ( 5a–5h ) has been synthesized, characterized by FT-IR, NMR spectroscopy and mass spectrometry and tested against human monoamine oxidase (MAO) A and B. Only (4-hydroxy-3-methoxybenzylidene) substituted compounds gave submicromolar inhibition of MAO-A and MAO-B. Changing the phenyl substituent to methyl on the unsaturated quinazoline ring ( 12a–12d ) decreased inhibition, but a less flexible linker ( 14a–14d ) resulted in selective micromolar inhibition of hMAO-B providing insight for ongoing design.

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).

scholarly journals Monoamine Oxidase Inhibitory Activity of Biflavonoids from Branches of Garcinia gardneriana (Clusiaceae)

2017 ◽  
Vol 12 (4) ◽  
pp. 1934578X1701200 ◽  
Author(s):  
Maria Angélica Recalde-Gil ◽  
Luiz Carlos Klein-Júnior ◽  
Carolina dos Santos Passos ◽  
Juliana Salton ◽  
Sérgio Augusto de Loreto Bordignon ◽  
...  
Keyword(s):  
Monoamine Oxidase ◽  
Inhibitory Activity ◽  
Ethanol Extract ◽  
Ethyl Acetate Fraction ◽  
Spectrometric Data ◽  
Mao B ◽  
Inhibitory Compounds ◽  
Mao A ◽  
Mao Activity

Garcinia gardneriana is chemically characterized by the presence of biflavonoids. Taking into account that flavonoids are able to inhibit monoamine oxidase (MAO) activity, in the present study, the chemical composition of the branches’ extract of the plant is described for the first time and the MAO inhibitory activity of the isolated biflavonoids was evaluated. Based on spectroscopic and spectrometric data, it was possible to identify volkesiflavone, morelloflavone (1), Gb-2a (2) and Gb-2a-7- O-glucoside (3) in the ethyl acetate fraction from ethanol extract of the branches. Compounds 1-3 were evaluated in vitro and demonstrated the capacity to inhibit MAO-A activity with an IC50 ranging from 5.05 to 10.7 μM, and from 20.7 to 66.2 μM for MAO-B. These inhibitions corroborate with previous IC50 obtained for monomeric flavonoids, with a higher selectivity for MAO-A isoform. The obtained results indicate that biflavonoids might be promising structures for the identification of new MAO inhibitory compounds.

Trimethoxy Crown Chalcones as Multifunctional Class of Monoamine Oxidase Enzyme Inhibitors

2021 ◽  
Vol 24 ◽  
Author(s):  
Naseer Maliyakkal ◽  
Ipek Baysal ◽  
Anandkumar Tengli ◽  
Gulberk Ucar ◽  
Mohammad Ali Abdullah Almoyad ◽  
...  
Keyword(s):  
Monoamine Oxidase ◽  
Enzyme Inhibitors ◽  
Inhibition Constant ◽  
Docking Simulations ◽  
Mao B ◽  
Cytotoxicity Studies ◽  
Mao A ◽  
Oxidase Enzyme ◽  
Antioxidant Molecule

Background: Chalcones with methoxy substituents are considered as a promising framework for the inhibition of monoamine oxidase (MAO) enzymes. Methods: A series of nine trimethoxy substituted chalcones (TMa-TMi) was synthesized and evaluated as a multifunctional class of MAO inhibitors. All the synthesized compounds were investigated for their in vitro MAO inhibition, kinetics, reversibility, blood-brain barrier (BBB) permeation, and cytotoxicity and antioxidant potentials. Results: In the present study, compound (2E)-3-(4-nitrophenyl)-1-(3,4,5-trimethoxyphenyl)prop-2-en-1-one (TMf) was provided with an MAO-A inhibition constant value equal to 3.47±0.09 μM and with a selectivity of 0.008. Thus, it was comparable to that of moclobemide, a well known potent hMAO-A inhibitor (SI=0.010). Compound (2E)-3-(4-bromophenyl)-1-(3,4,5-trimethoxyphenyl)prop-2-en-1-one (TMh) showed good MAO-B inhibition, with an inhibition constant of 0.46±0.009 μM. The PAMPA assay demonstrated that all the synthesized derivatives can cross the BBB successfully. The cytotoxicity studies revealed that TMf and TMh have 88.22 and 80.18 % cell viability at 25 µM. Compound TMf appeared as the most promising antioxidant molecule with IC50 values, relative to DPPH and H2O2 radical activities, equal to 6.02±0.17 and 7.25±0.07 μM. To shed light on the molecular interactions of TMf and TMh towards MAO-A and MAO-B, molecular docking simulations and MM/GBSA calculations have been carried out. Conclusion: The lead molecules TMf and TMh with multi-functional nature can be further employed for the treatment of various neurodegenerative disorders and depressive states.

Synthesis, molecular modeling, and in vitro screening of monoamine oxidase inhibitory activities of some novel hydrazone derivatives

2013 ◽  
Vol 120 (6) ◽  
pp. 883-891 ◽  
Author(s):  
Umut Salgın-Gökşen ◽  
Nesrin Gökhan-Kelekçi ◽  
Samiye Yabanoglu-Çiftci ◽  
Kemal Yelekçi ◽  
Gülberk Uçar
Keyword(s):  
Molecular Modeling ◽  
Monoamine Oxidase ◽  
In Vitro Screening ◽  
Inhibitory Activities

scholarly journals Chasing ChEs-MAO B Multi-Targeting 4-Aminomethyl-7-Benzyloxy-2H-Chromen-2-ones

Molecules ◽  
2019 ◽  
Vol 24 (24) ◽  
pp. 4507 ◽  
Author(s):  
Mariagrazia Rullo ◽  
Marco Catto ◽  
Antonio Carrieri ◽  
Modesto de Candia ◽  
Cosimo Damiano Altomare ◽  
...  
Keyword(s):  
Monoamine Oxidase ◽  
Single Point ◽  
Monoamine Oxidase B ◽  
In Vitro Screening ◽  
Binding Modes ◽  
Kinetics Analysis ◽  
Docking Simulations ◽  
Mao B ◽  
Insight Into

A series of 4-aminomethyl-7-benzyloxy-2H-chromen-2-ones was investigated with the aim of identifying multiple inhibitors of cholinesterases (acetyl- and butyryl-, AChE and BChE) and monoamine oxidase B (MAO B) as potential anti-Alzheimer molecules. Starting from a previously reported potent MAO B inhibitor (3), we studied single-point modifications at the benzyloxy or at the basic moiety. The in vitro screening highlighted triple-acting compounds (6, 8, 9, 16, 20) showing nanomolar and selective MAO B inhibition along with IC50 against ChEs at the low micromolar level. Enzyme kinetics analysis toward AChE and docking simulations on the target enzymes were run in order to get insight into the mechanism of action and plausible binding modes.

Synthesis and in vitro Evaluation of 2-heteroarylidene-1-tetralone Derivatives as Monoamine Oxidase Inhibitors

Drug Research ◽  
2018 ◽  
Vol 68 (12) ◽  
pp. 687-695 ◽  
Author(s):  
Klaudia Amakali ◽  
Lesetja Legoabe ◽  
Anél Petzer ◽  
Jacobus Petzer
Keyword(s):  
Monoamine Oxidase ◽  
Potassium Hydroxide ◽  
Inhibition Activity ◽  
Mao B ◽  
Mao Inhibition ◽  
Mao A ◽  
Inhibition Studies ◽  
Inhibition Potencies ◽  
Substituted 1

AbstractThe present study investigates the human monoamine oxidase (MAO) inhibition properties of a series of twelve 2-heteroarylidene-1-tetralone derivatives. Also included are related cyclohexylmethylidene, cyclopentylmethylidene and benzylidene substituted 1-tetralones. These compounds are related to the 2-benzylidene-1-indanone class of compounds which has previously been shown to inhibit the MAOs, with specificity for the MAO-B isoform. The target compounds were synthesised by the Claisen-Schmidt condensation between 7-methoxy-1-tetralone or 1-tetralone, and various aldehydes, under acid (hydrochloric acid) or base (potassium hydroxide) catalysis. The results of the MAO inhibition studies showed that the 2-heteroarylidene-1-tetralone and related derivatives are in most instances more selective inhibitors of the MAO-B isoform compared to MAO-A. (2E)-2-Benzylidene-7-methoxy-3,4-dihydronaphthalen-1(2 H)-one (IC50=0.707 μM) was found to be the most potent MAO-B inhibitor, while the most potent MAO-A inhibitor was (2E)-2-[(2-chloropyridin-3-yl)methylidene]-7-methoxy-3,4-dihydronaphthalen-1(2 H)-one (IC50=1.37 μM). The effect of the heteroaromatic substituent on MAO-B inhibition activity, in decreasing order was found to be: cyclohexyl, phenyl>thiophene>pyridine, furane, pyrrole, cyclopentyl. This study concludes that, although some 2-heteroarylidene-1-tetralone derivatives are good potency MAO inhibitors, in general their inhibition potencies, particularly for MAO-B, are lower than structurally related chalcones and 1-indanone derivatives that were previously studied.

scholarly journals Design, synthesis, molecular docking, and in vitro α-glucosidase inhibitory activities of novel 3-amino-2,4-diarylbenzo[4,5]imidazo[1,2-a]pyrimidines against yeast and rat α-glucosidase

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Fariba Peytam ◽  
Ghazaleh Takalloobanafshi ◽  
Toktam Saadattalab ◽  
Maryam Norouzbahari ◽  
Zahra Emamgholipour ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Docking Study ◽  
Rat Small Intestine ◽  
Molecular Docking Study ◽  
Design Synthesis ◽  
Mild Conditions ◽  
Glucosidase Inhibitors ◽  
Inhibitory Activities

AbstractIn an attempt to find novel, potent α-glucosidase inhibitors, a library of poly-substituted 3-amino-2,4-diarylbenzo[4,5]imidazo[1,2-a]pyrimidines 3a–ag have been synthesized through heating a mixture of 2-aminobenzimidazoles 1 and α-azidochalcone 2 under the mild conditions. This efficient, facile protocol has been resulted into the desirable compounds with a wide substrate scope in good to excellent yields. Afterwards, their inhibitory activities against yeast α-glucosidase enzyme were investigated. Showing IC50 values ranging from 16.4 ± 0.36 µM to 297.0 ± 1.2 µM confirmed their excellent potency to inhibit α-glucosidase which encouraged us to perform further studies on α-glucosidase enzymes obtained from rat as a mammal source. Among various synthesized 3-amino-2,4-diarylbenzo[4,5]imidazo[1,2-a]pyrimidines, compound 3k exhibited the highest potency against both Saccharomyces cerevisiae α-glucosidase (IC50 = 16.4 ± 0.36 μM) and rat small intestine α-glucosidase (IC50 = 45.0 ± 8.2 μM). Moreover, the role of amine moiety on the observed activity was studied through substituting with chlorine and hydrogen resulted into a considerable deterioration on the inhibitory activity. Kinetic study and molecular docking study have confirmed the in-vitro results.

scholarly journals Design, Synthesis and Biological Evaluation of Novel Benzothiazole Based [1,2,4]Triazolo[4,3-c]quinazoline Derivatives

2020 ◽  
Vol 32 (3) ◽  
pp. 580-586
Author(s):  
Ranjit V. Gadhave ◽  
Bhanudas S. Kuchekar
Keyword(s):  
Biological Evaluation ◽  
Bacterial Strains ◽  
Active Compounds ◽  
Design Synthesis ◽  
Structural Modifications ◽  
E Coli ◽  
Chemical Structures ◽  
Ft Ir ◽  
Antioxidant Agent

A new series of N-(benzo[d]thiazol-2-yl)-[1,2,4]triazolo[4,3-c]quinazoline-5-carboxamide derivatives were synthesized by condensation of [1,2,4]triazolo[4,3-c]quinazoline-5-carboxylate derivatives with substituted benzothiazoles. The chemical structures of the synthesized compounds were confirmed by FT-IR, MS and 1H NMR spectra. Designed triazoloquinazoline derivatives were docked with oxido-reductase enzyme (PDB Code 4h1j) and DNA gyrase enzyme (PDB Code 3g75). Based on high binding affinity score, the best compound were selected for synthesis and subjected to in vitro antioxidant and antibacterial activity. Compounds 7a and 7d were found to be most active compounds as antioxidant agent among this series when compared with ascorbic acid. Compounds 7a, 7d and 7f were found to be most active compounds as an antibacterial agents among this series when compared with ciprofloxacin against bacterial strains such as S. aureus (ATCC 25923), E. coli (ATCC 25922) and P. aeruginosa (ATCC 27853). Study revealed that the most active compounds after structural modifications can be exploited as lead molecules for other pharmacological activities such as anti-inflammatory, anticancer and antidepressant activities.

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.

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