Full metadata record

DC FieldValueLanguage
dc.contributor.author박기덕-
dc.contributor.author박종현-
dc.contributor.author김시원-
dc.contributor.author김현지-
dc.contributor.author김현정-
dc.contributor.author엘리자 리-
dc.contributor.author최지원-
dc.contributor.author김병은-
dc.contributor.author유종석-
dc.contributor.author이용섭-
dc.date.accessioned2021-07-06T15:30:02Z-
dc.date.available2021-07-06T15:30:02Z-
dc.date.issued2021-02-
dc.identifier.citationVOL 212, 113103-
dc.identifier.issn0223-5234-
dc.identifier.other57071-
dc.identifier.urihttps://pubs.kist.re.kr/handle/201004/73388-
dc.description.abstractThe Kelch-like ECH-associated protein 1 (Keap1)-Nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway plays a pivotal role in the cellular defense system against oxidative stress by inducing antioxidant and anti-inflammatory effects. We previously developed Nrf2 activators that potentially protect the death of dopaminergic (DAergic) neuronal cells against oxidative stress in Parkinson’s disease (PD). In this study, we designed and synthesized a class of halogenated vinyl sulfones by inserting halogens and pyridine to maximize Nrf2 activation efficacy. Among the synthesized compounds, (E)-3-chloro-2-(2-((2-chlorophenyl)sulfonyl)vinyl)pyridine (9d) significantly exhibited potent Nrf2 activating efficacy (9d: EC50 = 26 nM) at least 10-fold compared with the previous developed compounds (1 and 2). Furthermore, treating with 9d remarkably increased Nrf2 nuclear translocation and Nrf2 protein levels in microglial BV-2 cells. 9d was shown to induce the expression of antioxidant response genes HO-1, GCLC, GCLM, and SOD-1 at both the mRNA and protein levels and suppress proinflammatory cytokines and enzymes. Also, 9d remarkably protected DAergic neurons and restored the PD-associated motor dysfunction in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model.-
dc.publisherEuropean journal of medicinal chemistry-
dc.titleDevelopment and optimization of halogenated vinyl sulfones as Nrf2 activators for the treatment of Parkinson's disease-
dc.typeArticle-
dc.relation.page113103-
Appears in Collections:
KIST Publication > Article
Files in This Item:
There are no files associated with this item.
Export
RIS (EndNote)
XLS (Excel)
XML


qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

BROWSE