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

被引：46

作者：

Huleatt, Paul B. ^{[1
]}

Khoo, Mui Ling ^{[1
]}

Chua, Yi Yuan ^{[1
]}

Tan, Tiong Wei ^{[1
]}

Liew, Rou Shen ^{[1
]}

Balogh, Balazs ^{[2
]}

Deme, Ruth ^{[2
]}

Goeloencser, Flora ^{[3
]}

Magyar, Kalman ^{[5
]}

Sheela, David P. ^{[4
]}

Ho, Han Kiat ^{[4
]}

Sperlagh, Beata ^{[3
]}

Matyus, Peter ^{[2
]}

Chai, Christina L. L. ^{[1
,4
]}

机构：

[1] ASTAR, Inst Chem & Engn Sci, Singapore 138665, Singapore

[2] Semmelweis Univ, Dept Organ Chem, H-1092 Budapest, Hungary

[3] Hungarian Acad Sci, Inst Expt Med, Dept Pharmacol, H-1083 Budapest, Hungary

[4] Natl Univ Singapore, Dept Pharm, Singapore 117543, Singapore

[5] Semmelweis Univ, Dept Pharmacodynam, H-1089 Budapest, Hungary

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2015年 / 58卷 / 03期

关键词：

PROTEIN-KINASE-C; COUPLING REACTIONS; IN-VITRO; RASAGILINE; DRUG; CHLORINATION; APOPTOSIS; ISOFORMS; ALKENES; BCL-2;

D O I：

10.1021/jm501722s

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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.

引用

页码：1400 / 1419

页数：20

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