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 language | English |
|---|---|
| Pages (from-to) | 4921-4935 |
| Number of pages | 15 |
| Journal | Bioorganic and Medicinal Chemistry |
| Volume | 20 |
| Issue number | 16 |
| DOIs | |
| Publication status | Published - 2012 Aug 15 |
Bibliographical note
Funding Information:We thank the Digital biotech scientists, Dr. Y.H. Kim and Ms. Hee Kim, for their support of biological assay data. This work was financially supported by Research Fund 2011 of The Catholic University of Korea .
Keywords
- Aggregation inhibitor
- Alzheimer disease
- Bis-styryl aromatic compound
- β-Amyloid
ASJC Scopus subject areas
- Biochemistry
- Molecular Medicine
- Molecular Biology
- Pharmaceutical Science
- Drug Discovery
- Clinical Biochemistry
- Organic Chemistry