Design, synthesis and anti-Alzheimer properties of dimethylaminomethyl-substituted curcumin derivatives

被引：54

作者：

Fang, Lei ^{[1
,2
,3
]}

Gou, Shaohua ^{[1
,2
]}

Liu, Xuying ^{[1
,2
]}

Cao, Feng ^{[3
]}

Cheng, Lin ^{[1
,2
]}

机构：

[1] Southeast Univ, Sch Chem & Chem Engn, Pharmaceut Res Ctr, Nanjing 211189, Jiangsu, Peoples R China

[2] Southeast Univ, Sch Chem & Chem Engn, Jiangsu Prov Hitech Key Lab Biomed Res, Nanjing 211189, Jiangsu, Peoples R China

[3] China Pharmaceut Univ, State Key Lab Nat Med, Nanjing 210009, Jiangsu, Peoples R China

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2014年 / 24卷 / 01期

基金：

中国国家自然科学基金;

关键词：

Curcumin derivatives; Antioxidant; A beta aggregation inhibition; Stability; Anti-Alzheimer; DISEASE; SOLUBILITY; MECHANISMS; STABILITY; PROBES;

D O I：

10.1016/j.bmcl.2013.12.011

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Eight dimethylaminomethyl-substituted curcumin derivatives were designed and synthesized. The antioxidant test revealed that the synthesized compounds had higher free radical scavenging activity towards both 2,2-diphenyl-1-picrylhydrazyl free radicals (DPPH) (IC50 1.5-29.9 mu M) and galvinoxyl radicals (IC50 4.9-41.1 mu M) than the lead compound curcumin. Besides, compound 3a could effectively inhibit the Ab self-aggregation in vitro. Investigated in phosphate-buffered solutions (pH = 7.4) in the presence or absence of 0.1% FBS 3a showed a good stability while curcumin did not. Furthermore, 3a showed a good lipophilicity (logP = 3.48), suggesting a potential ability to penetrate the blood-brain-barrier. The aqueous solubility of the hydrochloride salt of 3a (16.7 mg/mL) has also been significantly improved as compared with curcumin (< 0.1 mg/mL). (C) 2013 Elsevier Ltd. All rights reserved.

引用

页码：40 / 43

页数：4

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