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

• 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
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/jm501722s

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.