Sulfur-Substituted α-Alkyl Phenethylamines as Selective and Reversible MAO-A Inhibitors:  Biological Activities, CoMFA Analysis, and Active Site Modeling

Gallardo-Godoy, Alejandra; Fierro, Angélica; McLean, Thomas H.; Castillo, M.; Cassels, Bruce K.; Reyes‐Parada, Miguel; Nichols, David E.

doi:10.1021/jm0493109

Cited by 91 publications

(46 citation statements)

References 31 publications

(78 reference statements)

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“…9-11 Structure-activity relationship (SAR) studies, including quantitative analyses (QSAR), [10][11][12] have shown that the presence of electron-donating, unbranched, alkylthio substituents at the para position of the aromatic ring of the amphetamine scaffold generate potent and selective MAO-A inhibitors. In addition, a few studies have shown that the (S)-isomers of substituted amphetamines (which are always dextrorotatory) are the eutomers.…”

Section: Introductionmentioning

confidence: 99%

Human and rat monoamine oxidase-A are differentially inhibited by (S)-4-alkylthioamphetamine derivatives: Insights from molecular modeling studies

Fierro

Osorio

Cassels

et al. 2007

Bioorganic & Medicinal Chemistry

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Four enantiomerically pure (S)-4-alkylthioamphetamine derivatives were evaluated as monoamine oxidase (MAO) inhibitors using the human and rat isoforms of the enzyme. Molecular dockings were performed in order to gain insights regarding the binding mode of these inhibitors. All compounds were potent and selective MAO-A inhibitors although different rank orders of potencies were observed against the enzymes from different species. This behavior can be rationalized on the basis of different binding modes to each enzyme, as determined in silico. These findings further support the concept that MAO inhibitory activity of novel compounds, determined with enzymes from diverse mammalian species, should be considered with caution if human MAO is the final target to be addressed.

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Section: Introductionmentioning

confidence: 99%

Human and rat monoamine oxidase-A are differentially inhibited by (S)-4-alkylthioamphetamine derivatives: Insights from molecular modeling studies

Fierro

Osorio

Cassels

et al. 2007

Bioorganic & Medicinal Chemistry

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“…The 1 H NMR spectrum has been reported for the α-methyl homologue 4 of 2C-T in D2O, [48] and for the α-methyl, α-ethyl, and N-methyl homologues of the 2C-T series (and the Ψ-2C-T series 5 ) in D2O. [71] Trachsel has synthesized additional members of the 2C-T series and has reported their spectra in D2O. [72] 4 ALEPH or DOT: 1-[2,5-dimethoxy-4-(methylsulfanyl)phenyl]propan-2-amine.…”

Section: The 4-rs Family: 4-alkylsulfanyl-25-dimethoxyphenyl Patternmentioning

confidence: 99%

PeakAL: Protons I Have Known and Loved - Fifty Shades of Grey-Market Spectra

Chapman

Avanes²

2015

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“…4, structure 8) [128]. This scaffold is present in many catecholamine neurotransmitters and small variations in the structure can yield different biogenic amine target inhibitors [98,[129][130][131].…”

Section: Indole and Isatin Analogues-a Series Of Indole And Isatin Anmentioning

confidence: 99%

Predicting Monoamine Oxidase Inhibitory Activity Through Ligand-Based Models

Vilar¹,

Ferino²,

Quezada³

et al. 2013

CTMC

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The evolution of bio-and cheminformatics associated with the development of specialized software and increasing computer power has produced a great interest in theoretical in silico methods applied in drug rational design. These techniques apply the concept that "similar molecules have similar biological properties" that has been exploited in Medicinal Chemistry for years to design new molecules with desirable pharmacological profiles. Ligand-based methods are not dependent on receptor structural data and take into account two and three-dimensional molecular properties to assess similarity of new compounds in regards to the set of molecules with the biological property under study. Depending on the complexity of the calculation, there are different types of ligand-based methods, such as QSAR (Quantitative Structure-Activity Relationship) with 2D and 3D descriptors, CoMFA (Comparative Molecular Field Analysis) or pharmacophoric approaches. This work provides a description of a series of ligand-based models applied in the prediction of the inhibitory activity of monoamine oxidase (MAO) enzymes. The controlled regulation of the enzymes' function through the use of MAO inhibitors is used as a treatment in many psychiatric and neurological disorders, such as depression, anxiety, Alzheimer's and Parkinson's disease. For this reason, multiple scaffolds, such as substituted coumarins, indolylmethylamine or pyridazine derivatives were synthesized and assayed toward MAO-A and MAO-B inhibition. Our intention is to focus on the description of ligand-based models to provide new insights in the relationship between the MAO inhibitory activity and the molecular structure of the different inhibitors, and further study enzyme selectivity and possible mechanisms of action.

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Sulfur-Substituted α-Alkyl Phenethylamines as Selective and Reversible MAO-A Inhibitors: Biological Activities, CoMFA Analysis, and Active Site Modeling

Cited by 91 publications

References 31 publications

Human and rat monoamine oxidase-A are differentially inhibited by (S)-4-alkylthioamphetamine derivatives: Insights from molecular modeling studies

Human and rat monoamine oxidase-A are differentially inhibited by (S)-4-alkylthioamphetamine derivatives: Insights from molecular modeling studies

PeakAL: Protons I Have Known and Loved - Fifty Shades of Grey-Market Spectra

Predicting Monoamine Oxidase Inhibitory Activity Through Ligand-Based Models

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