Evaluation of the oxidation of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to toxic pyridinium cations by monoamine oxidase (MAO) enzymes and its use to search for new MAO inhibitors and protective agents

Herraiz, Tomás

doi:10.3109/14756366.2011.616946

Cited by 19 publications

(6 citation statements)

References 50 publications

(109 reference statements)

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“…MAO-A is found in the liver, gastrointestinal tract, and placenta, whereas MAO-B is found primarily in blood platelets. Leonardi and Azmitia, 1994;Kalgutkar and Castagnoli, 1995;Herraiz, 2009Herraiz, , 2012Geha et al, 2001 MAO-B b -phenylethylamine(2) (-) Deprenyl d * 0.0002-2 (IC 50 = 0.001) Geha et al, 2001;Herraiz, 2009Herraiz, , 2012FMO (1, 3, and 5) Benzydamine (FMO 1 = 24; FMO3 = 40)…”

Section: Identification Of Monoamine Oxidases Mao-a and Mao-bmentioning

confidence: 99%

Evaluation of a New Molecular Entity as a Victim of Metabolic Drug-Drug Interactions--an Industry Perspective

Bohnert¹,

Patel²,

Templeton³

et al. 2016

Drug Metabolism and Disposition

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Under the guidance of the International Consortium for Innovation and Quality in Pharmaceutical Development (IQ), scientists from 20 pharmaceutical companies formed a Victim Drug-Drug Interactions Working Group. This working group has conducted a review of the literature and the practices of each company on the approaches to clearance pathway identification (f CL ), estimation of fractional contribution of metabolizing enzyme toward metabolism (f m ), along with modeling and simulation-aided strategy in predicting the victim drug-drug interaction (DDI) liability due to modulation of drug metabolizing enzymes. Presented in this perspective are the recommendations from this working group on: 1) strategic and experimental approaches to identify f CL and f m , 2) whether those assessments may be quantitative for certain enzymes (e.g., cytochrome P450, P450, and limited uridine diphosphoglucuronosyltransferase, UGT enzymes) or qualitative (for most of other drug metabolism enzymes), and the impact due to the lack of quantitative information on the latter. Multiple decision trees are presented with stepwise approaches to identify specific enzymes that are involved in the metabolism of a given drug and to aid the prediction and risk assessment of drug as a victim in DDI. Modeling and simulation approaches are also discussed to better predict DDI risk in humans. Variability and parameter sensitivity analysis were emphasized when applying modeling and simulation to capture the differences within the population used and to characterize the parameters that have the most influence on the prediction outcome.

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Section: Identification Of Monoamine Oxidases Mao-a and Mao-bmentioning

confidence: 99%

Evaluation of a New Molecular Entity as a Victim of Metabolic Drug-Drug Interactions--an Industry Perspective

Bohnert¹,

Patel²,

Templeton³

et al. 2016

Drug Metabolism and Disposition

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show abstract

“…On the basis of above design principle, the MAO‐A‐specific TPFP F1 , as well as FD1 ( F1 ‐oxidized product, in red halo), was successfully synthesized and fully characterized (Figure C and the Supporting Information). The expected MAO‐A‐dependent two‐photon fluorescence turn‐on strategy of F1 is shown in Figure D; the initially non‐fluorescent F1 would first undergo MAO‐A‐catalyzed oxidization to OX F1 , followed by rapid conversion to FD1 (through chemical/enzymatic oxidation in the system). The introduction of pyridinium (a strong electron‐withdrawing moiety with good conjugation) in FD1 would result in the formation of a push–pull system around the naphthalene fluorophore, thus ensuring F1 ‐to‐ FD1 conversion to be highly fluorogenic (that is, turned on) and detectable by TPFM .…”

Section: Resultsmentioning

confidence: 99%

Rational Design of a Two‐Photon Fluorogenic Probe for Visualizing Monoamine Oxidase A Activity in Human Glioma Tissues

Fang

Zhang

et al. 2020

Angew Chem Int Ed

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Monoamine oxidases have two functionally distinct but structurally similar isoforms (MAO‐A and MAO‐B). The ability to differentiate them by using fluorescence detection/imaging technology is of significant biological relevance, but highly challenging with available chemical tools. Herein, we report the first MAO‐A‐specific two‐photon fluorogenic probe (F1), capable of selective imaging of endogenous MAO‐A enzymatic activities from a variety of biological samples, including MAO‐A‐expressing neuronal SY‐SY5Y cells, the brain of tumor‐bearing mice and human Glioma tissues by using two‐photon fluorescence microscopy (TPFM) with minimal cytotoxicity.

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“…MPTP/MPP + )conversion properties catalyzed by MAO-B. [12] Subsequent docking results of F1 with various crystallographic structures of MAO-A/-B (Table S1) confirmed what was earlier predicted (Supporting Information, Figure 1B, right bottom, and Figure S1);insharp contrast to U1/MAO-A structure,t he N-alkylated tetrahydropyridine in the docked F1/MAO-A complex was shown to have projected closer toward FAD, with ameasured distance of 3.5 between the pyridine nitrogen in F1 and C5 in FAD( Figure 1B,r ight bottom and Figure S1). In the docked F1/MAO-B structure on the other hand, the N,N-dimethyl group has oriented towards FAD, making F1 unsuitable as aM AO-B substrate.…”

Section: Resultsmentioning

confidence: 99%

Rational Design of a Two‐Photon Fluorogenic Probe for Visualizing Monoamine Oxidase A Activity in Human Glioma Tissues

Fang

Zhang

et al. 2020

Angewandte Chemie

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Monoamine oxidases have two functionally distinct but structurally similar isoforms (MAO-A and MAO-B). The ability to differentiate them by using fluorescence detection/ imaging technology is of significant biological relevance,b ut highly challenging with available chemical tools.H erein, we report the first MAO-A-specific two-photon fluorogenic probe (F1), capable of selective imaging of endogenous MAO-A enzymatic activities from av ariety of biological samples, including MAO-A-expressing neuronal SY-SY5Y cells,t he brain of tumor-bearing mice and human Glioma tissues by using two-photon fluorescence microscopy( TPFM) with minimal cytotoxicity.

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Evaluation of the oxidation of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to toxic pyridinium cations by monoamine oxidase (MAO) enzymes and its use to search for new MAO inhibitors and protective agents

Abstract: To cite this article: Tomás Herraiz (2012) Evaluation of the oxidation of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to toxic pyridinium cations by monoamine oxidase (MAO) enzymes and its use to search for new MAO inhibitors and protective agents, Journal of Enzyme Inhibition and

Cited by 19 publications

References 50 publications

Evaluation of a New Molecular Entity as a Victim of Metabolic Drug-Drug Interactions--an Industry Perspective

Evaluation of a New Molecular Entity as a Victim of Metabolic Drug-Drug Interactions--an Industry Perspective

Rational Design of a Two‐Photon Fluorogenic Probe for Visualizing Monoamine Oxidase A Activity in Human Glioma Tissues

Rational Design of a Two‐Photon Fluorogenic Probe for Visualizing Monoamine Oxidase A Activity in Human Glioma Tissues

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