Abstract
To develop novel neuroprotective agents, a library of novel arylalkenylpropargylamines was synthesized and tested for inhibitory activities against monoamine oxidases. From this, a number of highly potent and selective monoamine oxidase B inhibitors were identified. Selected compounds were also tested for neuroprotection in in vitro studies with PC-12 cells treated with 6-OHDA and rotenone, respectively. It was observed that some of the compounds tested yielded a marked increase in survival in PC-12 cells treated with the neurotoxins. This indicates that these propargylamines are able to confer protection against the effects of the toxins and may also be considered as novel disease-modifying anti-Parkinsonian agents, which are much needed for the therapy of Parkinson's disease.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cell Survival / drug effects
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Cells, Cultured
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Dose-Response Relationship, Drug
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Humans
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Mice
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Molecular Structure
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Monoamine Oxidase / metabolism*
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Monoamine Oxidase Inhibitors / chemical synthesis
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Monoamine Oxidase Inhibitors / chemistry
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Monoamine Oxidase Inhibitors / pharmacology*
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Neuroprotective Agents / chemical synthesis
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Neuroprotective Agents / chemistry
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Neuroprotective Agents / pharmacology*
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PC12 Cells
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Pargyline / analogs & derivatives*
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Pargyline / chemical synthesis
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Pargyline / chemistry
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Pargyline / pharmacology
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Parkinson Disease / drug therapy*
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Parkinson Disease / enzymology
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Parkinson Disease / metabolism
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Propylamines / chemical synthesis
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Propylamines / chemistry
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Propylamines / pharmacology*
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Rats
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Structure-Activity Relationship
Substances
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Monoamine Oxidase Inhibitors
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Neuroprotective Agents
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Propylamines
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propargylamine
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Pargyline
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Monoamine Oxidase