Development of a New Distyrylbenzene-Derivative Amyloid-β-aggregation and Fibril Formation Inhibitor

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Author(s)

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)<sub>3</sub>, 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)<sub>3</sub> 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)<sub>3</sub> disrupts clumps of Aβ protein and is a likely candidate for drug development to treat Alzheimer’s disease.

Journal

  • Chemical and Pharmaceutical Bulletin

    Chemical and Pharmaceutical Bulletin 60(9), 1164-1170, 2012

    The Pharmaceutical Society of Japan

Codes

  • NII Article ID (NAID)
    130001852537
  • NII NACSIS-CAT ID (NCID)
    AA00602100
  • Text Lang
    ENG
  • ISSN
    0009-2363
  • NDL Article ID
    023900163
  • NDL Call No.
    Z53-D167
  • Data Source
    NDL  J-STAGE 
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