scholarly journals Studies on 5-fluoro-.ALPHA.-methyltryptamine and p-chloro-.BETA.-methylphenethylamine: Determination of the MAO-A or MAO-B selective inhibition in vitro.

1988 ◽  
Vol 46 (2) ◽  
pp. 197-199 ◽  
Author(s):  
Hiroyasu KINEMUCHI ◽  
Yuichiro ARAI ◽  
Yoshie TOYOSHIMA ◽  
Takeshi TADANO ◽  
Kensuke KISARA
Keyword(s):  
Selective Inhibition ◽  
Mao B ◽  
Mao A

scholarly journals Studies on 5-Fluoro-α-Methyltryptamine and p-Chloro-β-Methylphenethylamine: Determination of the MAO-A or MAO-B Selective Inhibition In Vitro

1988 ◽  
Vol 46 (2) ◽  
pp. 197-199
Author(s):  
Hiroyasu KINEMUCHI ◽  
Yuichiro ARAI ◽  
Yoshie TOYOSHIMA ◽  
Takeshi TADANO ◽  
Kensuke KISARA
Keyword(s):  
Selective Inhibition ◽  
Mao B ◽  
Mao A

scholarly journals Selective Inhibition of Human Monoamine Oxidase B by Acacetin 7-Methyl Ether Isolated from Turnera diffusa (Damiana)

Molecules ◽  
2019 ◽  
Vol 24 (4) ◽  
pp. 810 ◽  
Author(s):  
Narayan Chaurasiya ◽  
Jianping Zhao ◽  
Pankaj Pandey ◽  
Robert Doerksen ◽  
Ilias Muhammad ◽  
...  
Keyword(s):  
Methyl Ether ◽  
Enzyme Inhibitor ◽  
Equilibrium Dialysis ◽  
Selective Inhibition ◽  
Standard Drug ◽  
Mao B ◽  
Turnera Diffusa ◽  
Mechanism Of Inhibition ◽  
Mao A

The investigation of the constituents that were isolated from Turnera diffusa (damiana) for their inhibitory activities against recombinant human monoamine oxidases (MAO-A and MAO-B) in vitro identified acacetin 7-methyl ether as a potent selective inhibitor of MAO-B (IC50 = 198 nM). Acacetin 7-methyl ether (also known as 5-hydroxy-4′, 7-dimethoxyflavone) is a naturally occurring flavone that is present in many plants and vegetables. Acacetin 7-methyl ether was four-fold less potent as an inhibitor of MAO-B when compared to acacetin (IC50 = 50 nM). However, acacetin 7-methyl ether was >500-fold selective against MAO-B over MAO-A as compared to only two-fold selectivity shown by acacetin. Even though the IC50 for inhibition of MAO-B by acacetin 7-methyl ether was ~four-fold higher than that of the standard drug deprenyl (i.e., SelegilineTM or ZelaparTM, a selective MAO-B inhibitor), acacetin 7-methyl ether’s selectivity for MAO-B over MAO-A inhibition was greater than that of deprenyl (>500- vs. 450-fold). The binding of acacetin 7-methyl ether to MAO-B was reversible and time-independent, as revealed by enzyme-inhibitor complex equilibrium dialysis assays. The investigation on the enzyme inhibition-kinetics analysis with varying concentrations of acacetin 7-methyl ether and the substrate (kynuramine) suggested a competitive mechanism of inhibition of MAO-B by acacetin 7-methyl ether with Ki value of 45 nM. The docking scores and binding-free energies of acacetin 7-methyl ether to the X-ray crystal structures of MAO-A and MAO-B confirmed the selectivity of binding of this molecule to MAO-B over MAO-A. In addition, molecular dynamics results also revealed that acacetin 7-methyl ether formed a stable and strong complex with MAO-B. The selective inhibition of MAO-B suggests further investigations on acacetin 7-methyl as a potential new drug lead for the treatment of neurodegenerative disorders, including Parkinson’s disease.

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.

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 Selective Interactions of O-Methylated Flavonoid Natural Products with Human Monoamine Oxidase-A and -B

Molecules ◽  
2020 ◽  
Vol 25 (22) ◽  
pp. 5358
Author(s):  
Narayan D. Chaurasiya ◽  
Jacob Midiwo ◽  
Pankaj Pandey ◽  
Regina N. Bwire ◽  
Robert J. Doerksen ◽  
...  
Keyword(s):  
Natural Products ◽  
Enzyme Inhibition ◽  
Selective Inhibition ◽  
Monoamine Oxidase A ◽  
Inhibition Kinetics ◽  
Free Energies ◽  
Mao B ◽  
Mao A ◽  
Enzyme Inhibition Kinetics ◽  
Binding Free Energies

A set of structurally related O-methylated flavonoid natural products isolated from Senecio roseiflorus (1), Polygonum senegalense (2 and 3), Bhaphia macrocalyx (4), Gardenia ternifolia (5), and Psiadia punctulata (6) plant species were characterized for their interaction with human monoamine oxidases (MAO-A and -B) in vitro. Compounds 1, 2, and 5 showed selective inhibition of MAO-A, while 4 and 6 showed selective inhibition of MAO-B. Compound 3 showed ~2-fold selectivity towards inhibition of MAO-A. Binding of compounds 1–3 and 5 with MAO-A, and compounds 3 and 6 with MAO-B was reversible and not time-independent. The analysis of enzyme-inhibition kinetics suggested a reversible-competitive mechanism for inhibition of MAO-A by 1 and 3, while a partially-reversible mixed-type inhibition by 5. Similarly, enzyme inhibition-kinetics analysis with compounds 3, 4, and 6, suggested a competitive reversible inhibition of MAO-B. The molecular docking study suggested that 1 selectively interacts with the active-site of human MAO-A near N5 of FAD. The calculated binding free energies of the O-methylated flavonoids (1 and 4–6) and chalcones (2 and 3) to MAO-A matched closely with the trend in the experimental IC50′s. Analysis of the binding free-energies suggested better interaction of 4 and 6 with MAO-B than with MAO-A. The natural O-methylated flavonoid (1) with highly potent inhibition (IC50 33 nM; Ki 37.9 nM) and >292 fold selectivity against human MAO-A (vs. MAO-B) provides a new drug lead for the treatment of neurological disorders.

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.

scholarly journals Annurca Apple Polyphenol Extract Affects Acetyl- Cholinesterase and Mono-Amine Oxidase In Vitro Enzyme Activity

2021 ◽  
Vol 14 (1) ◽  
pp. 62
Author(s):  
Rosarita Nasso ◽  
Valentina Pagliara ◽  
Stefania D’Angelo ◽  
Rosario Rullo ◽  
Mariorosario Masullo ◽  
...  
Keyword(s):  
Enzyme Activity ◽  
Neurodegenerative Disorders ◽  
Amine Oxidase ◽  
Biological Properties ◽  
Human Neuroblastoma ◽  
Mao B ◽  
Brain Functions ◽  
Mao A ◽  
Ic50 Values

In this study, we explored the ability of Annurca apple flesh polyphenol extract (AFPE) to affect the activity of key enzymes involved in neurodegenerative disorders—in particular, Acetyl- and Butirryl-cholinesterases, and type A and B monoamine oxidase. The effect of AFPE on enzyme activity was analyzed by in vitro enzyme assays, and the results showed concentration-dependent enzyme inhibition, with IC50 values corresponding to 859 ± 18 µM and 966 ± 72 µM for AChE and BuChE respectively, and IC50 corresponding to 145 ± 3 µM and 199 ± 7 µM for MAO-A and MAO-B, respectively, with a preference for MAO-A. Moreover, in this concentration range, AFPE did not affect the viability of human neuroblastoma SH-SY5Y and fibroblast BJ-5ta cell lines, as determined by an MTT assay. In conclusion, our results demonstrate that AFPE shows the new biological properties of inhibiting the activity of enzymes that are involved in brain functions, neurodegenerative disorders, and aging.

scholarly journals Monoamine Oxidase Inhibition by Kavalactones from Kava (Piper Methysticum)

Planta Medica ◽  
2019 ◽  
Vol 85 (14/15) ◽  
pp. 1136-1142
Author(s):  
Denise Prinsloo ◽  
Sandra van Dyk ◽  
Anél Petzer ◽  
Jacobus P. Petzer
Keyword(s):  
Enzyme Inhibitor ◽  
Dissociation Constants ◽  
Piper Methysticum ◽  
Experimental Conditions ◽  
Mao Inhibitor ◽  
Mao B ◽  
Mao Inhibition ◽  
Mao A ◽  
Ic50 Values

AbstractMonoamine oxidases (MAOs) are key metabolic enzymes for neurotransmitter and dietary amines and are targets for the treatment of neuropsychiatric and neurodegenerative disorders. This study examined the MAO inhibition potential of kavain and other kavalactones from the roots of kava (Piper methysticum), a plant that has been used for its anxiolytic properties. (±)-Kavain was found to be a good potency in vitro inhibitor of human MAO-B with an IC50 of 5.34 µM. (±)-Kavain is a weaker MAO-A inhibitor with an IC50 of 19.0 µM. Under the same experimental conditions, the reference MAO inhibitor, curcumin, displays IC50 values of 5.01 µM and 2.55 µM for the inhibition of MAO-A and MAO-B, respectively. It was further established that (±)-kavain interacts reversibly and competitively with MAO-A and MAO-B with enzyme-inhibitor dissociation constants (Ki) of 7.72 and 5.10 µM, respectively. Curcumin in turn, displays a Ki value of 3.08 µM for the inhibition of MAO-A. Based on these findings, other kavalactones (dihydrokavain, methysticin, dihydromethysticin, yangonin, and desmethoxyyangonin) were also evaluated as MAO inhibitors in this study. Yangonin proved to be the most potent MAO inhibitor with IC50 values of 1.29 and 0.085 µM for MAO-A and MAO-B, respectively. It may be concluded that some of the central effects (e.g., anxiolytic) of kava may be mediated by MAO inhibition.

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