Bis-styrylpyridine and bis-styrylbenzene derivatives as inhibitors for Aβ fibril formation

被引：35

作者：

Byeon, Seong Rim

Lee, Ji Hoon

Sohn, Ji-Hoon

Kim, Dong Chan

Shin, Kye Jung

Yoo, Kyung Ho

Mook-Jung, Inhee

Lee, Won Koo

Kim, Dong Jin

机构：

[1] Korea Adv Inst Sci & Technol, Med Chem Res Ctr, Seoul 130650, South Korea

[2] Sogang Univ, Dept Chem, Seoul 121742, South Korea

[3] Sogang Univ, Interdisciplinary Prog Integrated Biotechnol, Seoul 121742, South Korea

[4] Seoul Natl Univ, Coll Med, Dept Biochem, Seoul 110799, South Korea

[5] Seoul Natl Univ, Coll Med, Inst Canc Res, Seoul 110799, South Korea

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2007年 / 17卷 / 05期

关键词：

A beta fibril formation inhibitor; Alzheimer disease; bis-styrylpyridine; bis-styrylbenzene; amyloid beta;

D O I：

10.1016/j.bmcl.2006.10.090

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

New bis-styrylpyridine and bis-styrylbenzene derivatives were designed and synthesized. These 34 compounds were evaluated by A beta fibril formation inhibitory assay using thioflavin T as a dye (named ThT assay). Most of them showed excellent inhibitory activities for A beta fibril formation at IC50 of 0.1-2.7 mu M which is comparable to curcumin (IC50 of 0.8 mu M). Among them, nine compounds were screened for their cytotoxicities on HT-22 cell by MTT assay at 1, 10, and 50 mu M. In particular, 1-7 and II-2 exhibited the best combination of inhibitory activity and compound cytotoxicity. (c) 2006 Elsevier Ltd. All rights reserved.

引用

收藏

页码：1466 / 1470

页数：5

相关论文

共 18 条

[1] Safety and anti-inflammatory activity of curcumin:: A component of tumeric (Curcuma longa) [J].

Chainani-Wu, N .

JOURNAL OF ALTERNATIVE AND COMPLEMENTARY MEDICINE, 2003, 9 (01) :161-168

[2] Review of the next generation of Alzheimer's disease therapeutics: Challenges for drug development [J].

Cutler, NR ;

Sramek, JJ .

PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY, 2001, 25 (01) :27-57

[3] Novel therapeutic strategies provide the real test for the amyloid hypothesis of Alzheimer's disease [J].

Dominguez, DI ;

De Strooper, B .

TRENDS IN PHARMACOLOGICAL SCIENCES, 2002, 23 (07) :324-330

[4] Prevention of transthyretin amyloid disease by changing protein misfolding energetics [J].

Hammarström, P ;

Wiseman, RL ;

Powers, ET ;

Kelly, JW .

SCIENCE, 2003, 299 (5607) :713-716

[5] Medicine - The amyloid hypothesis of Alzheimer's disease: Progress and problems on the road to therapeutics [J].

Hardy, J ;

Selkoe, DJ .

SCIENCE, 2002, 297 (5580) :353-356

[6] α-synuclein, especially the Parkinson's disease-associated mutants, forms pore-like annular and tubular protofibrils [J].

Lashuel, HA ;

Petre, BM ;

Wall, J ;

Simon, M ;

Nowak, RJ ;

Walz, T ;

Lansbury, PT .

JOURNAL OF MOLECULAR BIOLOGY, 2002, 322 (05) :1089-1102

[7] Isomerization of (Z,Z) to (E,E) 1-bromo-2,5-bis-(3-hydroxycarbonyl-4-hydroxy)styrylbenzene in strong base:: Probes for amyloid plaques in the brain [J].

Lee, CW ;

Zhuang, ZP ;

Kung, MP ;

Plössl, K ;

Skovronsky, D ;

Gur, T ;

Hou, C ;

Trojanowski, JQ ;

Lee, WMY ;

Kung, HF .

JOURNAL OF MEDICINAL CHEMISTRY, 2001, 44 (14) :2270-2275

[8] A hybrid molecule that prohibits amyloid fibrils and alleviates neuronal toxicity induced by β-amyloid (1-42) [J].

Lee, KH ;

Shin, BH ;

Shin, KJ ;

Kim, DJ ;

Yu, J .

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2005, 328 (04) :816-823

[9] Imaging β-amyloid plaques and neurofibrillary tangles in the aging human brain [J].

Mathis, CA ;

Wang, Y ;

Klunk, WE .

CURRENT PHARMACEUTICAL DESIGN, 2004, 10 (13) :1469-1492

[10] Extracellular amyloid formation and associated pathology in neural grafts [J].

Meyer-Luehmann, M ;

Stalder, M ;

Herzig, MC ;

Kaeser, SA ;

Kohler, E ;

Pfeifer, M ;

Boncristiano, S ;

Mathews, PM ;

Mercken, M ;

Abramowski, D ;

Staufenbiel, M ;

Jucker, M .

NATURE NEUROSCIENCE, 2003, 6 (04) :370-377