Synthesis and evaluation of biaryl derivatives for structural characterization of selective monoamine oxidase B Inhibitors toward Parkinson’s disease therapy

Title
Synthesis and evaluation of biaryl derivatives for structural characterization of selective monoamine oxidase B Inhibitors toward Parkinson’s disease therapy
Authors
배애님박기덕박종현최지원연슬기신수정김현정김시원이예림장보고반용선한균희이용섭
Issue Date
2018-01
Publisher
Bioorganic & medicinal chemistry
Citation
VOL 26, NO 1-244
Abstract
Benzyloxyphenyl moiety is a common structure of highly potent, selective and reversible inhibitors of monoamine oxidase B (MAO-B), safinamide and sembragiline. We synthesized 4-(benzyloxy)phenyl and biphenyl-4-yl derivatives including halogen substituents on the terminal aryl unit. In addition, we modified the carbon linker between amine group and the biaryl linked unit. Among synthesized compounds, 12c exhibited the most potent and selective MAO-B inhibitory effect (hMAO-B IC50: 8.9 nM; >10,000-fold selectivity over MAO-A) as a competitive inhibitor. In addition, 12c showed greater MAOB inhibitory activity and selectivity compared to well-known MAO-B inhibitors such as selegiline, safinamide and sembragiline. In the MPTP-induced mouse model of Parkinson’s disease (PD), 12c significantly protected the tyrosine hydroxylase (TH)-immunopositive DAergic neurons and attenuated the PD-associated behavioral deficits. This study suggests characteristic structures as a MAO-B inhibitor that may provide a good insight for the development of therapeutic agents for PD.
URI
http://pubs.kist.re.kr/handle/201004/67323
ISSN
0968-0896
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KIST Publication > Article
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