Development of a New Distyrylbenzene-Derivative Amyloid-β-aggregation and Fibril Formation Inhibitor
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- Suzuki Hideharu
- Faculty of Pharmaceutical Sciences, Toho University
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- Ishigami Akihito
- Molecular Regulation of Aging, Tokyo Metropolitan Institute of Gerontology
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- Orimoto Ayako
- Faculty of Pharmaceutical Sciences, Toho University
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- Matsuyama Akihiro
- Faculty of Pharmaceutical Sciences, Toho University
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- Handa Setsuko
- Molecular Regulation of Aging, Tokyo Metropolitan Institute of Gerontology
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- Maruyama Naoki
- Molecular Regulation of Aging, Tokyo Metropolitan Institute of Gerontology
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- Yokoyama Yuusaku
- Faculty of Pharmaceutical Sciences, Toho University
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- Okuno Hiroaki
- Faculty of Pharmaceutical Sciences, Toho University
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- Nakakoshi Masamichi
- Faculty of Pharmaceutical Sciences, Toho University
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Abstract
Several new amyloid-β (Aβ) aggregation inhibitors were synthesized according to our theory that a hydrophilic moiety could be attached to the Aβ-recognition unit for the purpose of preventing amyloid plaque formation. A distyrylbenzene-derivative, DSB(EEX)3, which consider the Aβ recognition unit (DSB, 1,4-distyrylbenzene) and expected to bind to amyloid fibrils (β-sheet structure), was combined with the hydrophilic aggregation disrupting element (EEX) (E, Glu; X, 2-(2-(2-aminoethoxy)ethoxy)acetic acid). This DSB(EEX)3 compound, compared to several others synthesized similarly, was found to be the most active for reducing Aβ toxicity toward IMR-32 human neuroblastoma cells. Moreover, its inhibition of Aβ-aggregation or fibril formation was directly confirmed by transmission electron microscopy and atomic force microscopy. These results suggest that the Aβ aggregation inhibitor DSB(EEX)3 disrupts clumps of Aβ protein and is a likely candidate for drug development to treat Alzheimer’s disease.
Journal
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- Chemical and Pharmaceutical Bulletin
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Chemical and Pharmaceutical Bulletin 60 (9), 1164-1170, 2012
The Pharmaceutical Society of Japan
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Details 詳細情報について
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- CRID
- 1390282679155831552
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- NII Article ID
- 130001852537
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- NII Book ID
- AA00602100
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- COI
- 1:STN:280:DC%2BC38bmvVSmsg%3D%3D
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- ISSN
- 13475223
- 00092363
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- NDL BIB ID
- 023900163
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- PubMed
- 22976325
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- Text Lang
- en
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- Data Source
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- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
- KAKEN
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- Abstract License Flag
- Disallowed