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Vallejos, Gabriel; Rezende, Marcos Caroli; Cassels, Bruce K.

doi:10.1023/a:1016344030772

Cited by 22 publications

(11 citation statements)

References 13 publications

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“…Accordingly, a handful of QSAR studies have shown that electronic features of the benzene ring (e.g. CHELPG atomic charges, HOMO energies) are the most important factors to determine the affinity of AMPH derivatives for MAO-A, and hence that their variation caused by substituents can greatly modulate their potency as enzyme inhibitors (Norinder et al, 1994;Vallejos et al, 2002;Fresqui et al, 2013). In this respect, the presence of a single substituent with electron-donor properties (e.g.…”

Section: Aromatic Ring Substitutionmentioning

confidence: 99%

Amphetamine Derivatives as Monoamine Oxidase Inhibitors

2020

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Amphetamine and its derivatives exhibit a wide range of pharmacological activities, including psychostimulant, hallucinogenic, entactogenic, anorectic, or antidepressant effects. The mechanisms of action underlying these effects are usually related to the ability of the different amphetamines to interact with diverse monoamine transporters or receptors. Moreover, many of these compounds are also potent and selective monoamine oxidase inhibitors. In the present work, we review how structural modifications on the aromatic ring, the amino group and/or the aliphatic side chain of the parent scaffold, modulate the enzyme inhibitory properties of hundreds of amphetamine derivatives. Furthermore, we discuss how monoamine oxidase inhibition might influence the pharmacology of these compounds.

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Section: Aromatic Ring Substitutionmentioning

confidence: 99%

Amphetamine Derivatives as Monoamine Oxidase Inhibitors

2020

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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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“…3, structure 4) [96]. All molecules were optimized geometrically and HOMO energies and charges on the aromatic carbons were calculated using AM1 method [97].…”

Section: Prediction Of Mao Activity Through 3d Ligand-based Modelsmentioning

confidence: 99%

Predicting Monoamine Oxidase Inhibitory Activity Through Ligand-Based Models

Vilar

Ferino²,

Quezada³

et al. 2012

Current Topics in Medicinal Chemistry

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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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Untitled

Cited by 22 publications

References 13 publications

Amphetamine Derivatives as Monoamine Oxidase Inhibitors

Amphetamine Derivatives as Monoamine Oxidase Inhibitors

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

Predicting Monoamine Oxidase Inhibitory Activity Through Ligand-Based Models

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