当前位置： SCI文献检索 > EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY期刊下所有文献 > 2,4-Disubstituted quinazolines as amyloid-β aggregation inhibitors with dual cholinesterase inhibition and antioxidant properties: Development and structure-activity relationship (SAR) studies.

2,4-Disubstituted quinazolines as amyloid-β aggregation inhibitors with dual cholinesterase inhibition and antioxidant properties: Development and structure-activity relationship (SAR) studies.

Abstract：

:A library of fifty-seven 2,4-disubstituted quinazoline derivatives were designed, synthesized and evaluated as a novel class of multi-targeting agents to treat Alzheimer's disease (AD). The biological assay results demonstrate the ability of several quinazoline derivatives to inhibit both acetyl and butyrylcholinesterase (AChE and BuChE) enzymes (IC50 range = 1.6-30.5 μM), prevent beta-amyloid (Aβ) aggregation (IC50 range 270 nM-16.7 μM) and exhibit antioxidant properties (34-63.4% inhibition at 50 μM). Compound 9 (N2-(1-benzylpiperidin-4-yl)-N4-(3,4-dimethoxybenzyl)quinazoline-2,4-diamine) was identified as a dual inhibitor of cholinesterases (AChE IC50 = 2.1 μM; BuChE IC50 = 8.3 μM) and exhibited good inhibition of Aβ aggregation (Aβ40 IC50 = 2.3 μM). Compound 15b (4-(benzylamino)quinazolin-2-ol) was the most potent Aβ aggregation inhibitor (Aβ40 IC50 = 270 nM) and was ∼4 and 1.4-fold more potent compared to the reference agents curcumin and resveratrol. These comprehensive structure activity-relationship (SAR) studies demonstrate the application of a 2,4-disubstituted quinazoline ring as a suitable template to develop multi-targeting agents to treat AD.

journal_name

Eur J Med Chem

journal_title

European journal of medicinal chemistry

authors

Mohamed T,Rao PPN

doi

10.1016/j.ejmech.2016.12.005

subject

Has Abstract

pub_date

2017-01-27 00:00:00

pages

823-843

eissn

0223-5234

issn

1768-3254

pii

S0223-5234(16)31011-X

journal_volume

126

pub_type

杂志文章

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