Novel Arylalkenylpropargylamines as Neuroprotective, Potent, and Selective Monoamine Oxidase B Inhibitors for the Treatment of Parkinson’s Disease

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 test...

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Bibliographic Details
Published in:	Journal of medicinal chemistry Vol. 58; no. 3; pp. 1400 - 1419
Main Authors:	Huleatt, Paul B, Khoo, Mui Ling, Chua, Yi Yuan, Tan, Tiong Wei, Liew, Rou Shen, Balogh, Balázs, Deme, Ruth, Gölöncsér, Flóra, Magyar, Kalman, Sheela, David P, Ho, Han Kiat, Sperlágh, Beáta, Mátyus, Péter, Chai, Christina L. L
Format:	Journal Article
Language:	English
Published:	United States American Chemical Society 12-02-2015
Subjects:	Animals Cell Survival - drug effects Cells, Cultured Dose-Response Relationship, Drug Humans Mice Molecular Structure Monoamine Oxidase - metabolism Monoamine Oxidase Inhibitors - chemical synthesis Monoamine Oxidase Inhibitors - chemistry Monoamine Oxidase Inhibitors - pharmacology Neuroprotective Agents - chemical synthesis Neuroprotective Agents - chemistry Neuroprotective Agents - pharmacology Pargyline - analogs & derivatives Pargyline - chemical synthesis Pargyline - chemistry Pargyline - pharmacology Parkinson Disease - drug therapy Parkinson Disease - enzymology Parkinson Disease - metabolism PC12 Cells Propylamines - chemical synthesis Propylamines - chemistry Propylamines - pharmacology Rats Structure-Activity Relationship
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Summary:	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.
ISSN:	0022-2623 1520-4804
DOI:	10.1021/jm501722s