Pyrazinyl ureas revisited: 1-(3-(Benzyloxy)pyrazin-2-yl)-3-(3,4-dichlorophenyl)urea, a new blocker of A beta-induced mPTP opening for Alzheimer's disease

Title
Pyrazinyl ureas revisited: 1-(3-(Benzyloxy)pyrazin-2-yl)-3-(3,4-dichlorophenyl)urea, a new blocker of A beta-induced mPTP opening for Alzheimer's disease
Authors
배애님노은주백소라Elkamhawy AhmedJung-eun ParkAhmed H.E. HassanJiyoun LeeBeoung-Geon Park
Issue Date
2018-09
Publisher
European journal of medicinal chemistry
Citation
VOL 157-278
Abstract
Herein, we report synthesis and evaluation of new twenty-eight pyrazinyl ureas against β amyloid (Aβ)-induced opening of mitochondrial permeability transition pore (mPTP) using JC-1 assay which measures the change of mitochondrial membrane potential (ΔΨm). The neuroprotective effect of seventeen compounds against Aβ-induced mPTP opening was superior to that of the standard Cyclosporin A (CsA). Among them, 1-(3-(benzyloxy)pyrazin-2-yl)-3-(3,4-dichlorophenyl)urea (5) effectively maintained mitochondrial function and cell viabilities on ATP assay and MTT assay. Also, hERG channel assay presented safe cardiotoxicity profile for compound 5. In addition, using CDocker algorithm, a molecular docking model presented a plausible explanation for the elicited differences in efficiencies of the synthesized compounds to reduce the green to red fluorescence as indication of mPTP closure. Hence, this report presents compound 5 as the most promising pyrazinyl urea-based mPTP blocker up to date.
URI
http://pubs.kist.re.kr/handle/201004/69789
ISSN
0223-5234
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KIST Publication > Article
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