Small molecules that protect against β-amyloid-induced cytotoxicity by inhibiting aggregation of β-amyloid

Yun Suk Lee, Hye Yun Kim, Youngsoo Kim, Jae Hong Seo, Eun Joo Roh, Hogyu Han, Kye Jung Shin

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Aggregated β-amyloid (Aβ) plays crucial roles in Alzheimer's disease (AD) pathogenesis, therefore blockade of Aβ aggregation is considered as a potential therapeutic target. We designed and synthesized small molecules to reduce Aβ-induced cytotoxicity by inhibiting Aβ aggregation. The small molecules were screened via ThT, MTT, and cell-based cytotoxicity assay (Aβ burden assay). Selected compounds 1c, 1d, 1e, and 1f were then investigated by evaluating their effects on cognitive impairment of acute AD mice model. Learning and memory dysfunction by injection of Aβ(1-42) was recovered by administration of these molecules. Especially, 1d showed the best recovery activity in Y-maze task, object recognition task, and passive avoidance task with dose dependent manner. These results suggest that 1d has high potential as a therapeutic agent for AD.

Original languageEnglish
Pages (from-to)4921-4935
Number of pages15
JournalBioorganic and Medicinal Chemistry
Volume20
Issue number16
DOIs
Publication statusPublished - 2012 Aug 15

Fingerprint

Cytotoxicity
Amyloid
Alzheimer Disease
Agglomeration
Molecules
Assays
Object recognition
Acute Disease
Learning
Data storage equipment
Recovery
Injections
Therapeutics

Keywords

  • β-Amyloid
  • Aggregation inhibitor
  • Alzheimer disease
  • Bis-styryl aromatic compound

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Drug Discovery
  • Organic Chemistry
  • Molecular Medicine
  • Molecular Biology
  • Clinical Biochemistry
  • Biochemistry

Cite this

Small molecules that protect against β-amyloid-induced cytotoxicity by inhibiting aggregation of β-amyloid. / Lee, Yun Suk; Kim, Hye Yun; Kim, Youngsoo; Seo, Jae Hong; Roh, Eun Joo; Han, Hogyu; Shin, Kye Jung.

In: Bioorganic and Medicinal Chemistry, Vol. 20, No. 16, 15.08.2012, p. 4921-4935.

Research output: Contribution to journalArticle

Lee, Yun Suk ; Kim, Hye Yun ; Kim, Youngsoo ; Seo, Jae Hong ; Roh, Eun Joo ; Han, Hogyu ; Shin, Kye Jung. / Small molecules that protect against β-amyloid-induced cytotoxicity by inhibiting aggregation of β-amyloid. In: Bioorganic and Medicinal Chemistry. 2012 ; Vol. 20, No. 16. pp. 4921-4935.
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