51 0

Chemistry-oriented synthesis (ChOS) and target deconvolution on neuroprotective effect of a novel scaffold, oxaza spiroquinone

Title
Chemistry-oriented synthesis (ChOS) and target deconvolution on neuroprotective effect of a novel scaffold, oxaza spiroquinone
Author
하정미
Keywords
1,5-oxaza spiroquinone; Chemistry-oriented synthesis; Neurodegenerative; NO inhibitory effect; JNK; DAPK; Molecular docking simulation; Y-maze test
Issue Date
2019-02
Publisher
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
Citation
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, v. 163, Page. 453-480
Abstract
Here we first time report an unprecedented and unnatural six-membered 1,5-oxaza spiroquinone scaffold with structural novelty, a convenient and efficient synthetic route was developed for the synthesis of new 1,5-oxaza spiroquinone derivatives (1a-1r) in high yields from readily available starting materials. The logic of the present work consists of (1) the identification of a promising unprecedented scaffold from privileged scaffolds of biological active molecules through our 'Chemistry-oriented Synthesis' (ChOS) approach, a compensatory strategy for target-based drug discovery, (2) the positioning of the identified 1,5-oxaza spiroquinone scaffold on neuroinflammation and neurodegenerative disease through nitric oxide (NO) inhibitory activity without cytotoxicity in hyper-activated microglia (IC50 of NO production: 0.07-1.82 mu M) to establish structure-activity relationship (SAR), (3) the investigation on the possibility as a selective kinase inhibitor related to neurodegenerative diseases (eg. JNK1, CDK2, DAPK1) through kinase full panel screening of the most potent compound 1n, and (4) the evaluation on in vivo efficacy of the compound 1n through Y-maze test. (C) 2018 Elsevier Masson SAS. All rights reserved.
URI
https://www.sciencedirect.com/science/article/pii/S0223523418309966https://repository.hanyang.ac.kr/handle/20.500.11754/112371
ISSN
0223-5234; 1768-3254
DOI
10.1016/j.ejmech.2018.11.037
Appears in Collections:
COLLEGE OF PHARMACY[E](약학대학) > PHARMACY(약학과) > Articles
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