Development of a new distyrylbenzene-derivative amyloid-ß-aggregation and fibril formation inhibitor.
Chem Pharm Bull (Tokyo)
; 60(9): 1164-70, 2012.
Article
en En
| MEDLINE
| ID: mdl-22976325
ABSTRACT
Several new amyloid-ß (Aß) aggregation inhibitors were synthesized according to our theory that a hydrophilic moiety could be attached to the Aß-recognition unit for the purpose of preventing amyloid plaque formation. A distyrylbenzene-derivative, DSB(EEX)(3), which consider the Aß recognition unit (DSB, 1,4-distyrylbenzene) and expected to bind to amyloid fibrils (ß-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 Aß toxicity toward IMR-32 human neuroblastoma cells. Moreover, its inhibition of Aß-aggregation or fibril formation was directly confirmed by transmission electron microscopy and atomic force microscopy. These results suggest that the Aß aggregation inhibitor DSB(EEX)(3) disrupts clumps of Aß protein and is a likely candidate for drug development to treat Alzheimer's disease.
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Bases de datos:
MEDLINE
Asunto principal:
Estirenos
/
Péptidos beta-Amiloides
/
Enfermedad de Alzheimer
/
Amiloide
Límite:
Humans
Idioma:
En
Revista:
Chem Pharm Bull (Tokyo)
Año:
2012
Tipo del documento:
Article
País de afiliación:
Japón