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- Title
- Development of curcumin-based amyloid β aggregation inhibitors for Alzheimer's disease using the SAR matrix approach
- Author(s)
- R Y Utomo; Y Asawa; S Okada; Hyun Seung Ban; A Yoshimori; J Bajorath; H Nakamura
- Bibliographic Citation
- Bioorganic & Medicinal Chemistry, vol. 46, pp. 116357-116357
- Publication Year
- 2021
- Abstract
- Amyloid β (Aβ) aggregation inhibitor activity cliff involving a curcumin structure was predicted using the SAR Matrix method on the basis of 697 known Aβ inhibitors from ChEMBL (data set 2487). Among the compounds predicted, compound B was found to possess approximately 100 times higher inhibitory activity toward Aβ aggregation than curcumin. TEM images indicate that compound B induced the shortening of Aβ fibrils and increased the generation of Aβ oligomers in a concentration dependent manner. Furthermore, compound K, in which the methyl ester of compound B was replaced by the tert-butyl ester, possessed low cytotoxicity on N2A cells and attenuated Aβ-induced cytotoxicity, indicating that compound K would have an ability for preventing neurotoxicity caused by Aβ aggregation.
- Keyword
- SAR matrixCurcuminAmyloid βAlzheimer’s diseaseNeurotoxicity
- ISSN
- 0968-0896
- Publisher
- Elsevier
- DOI
- http://dx.doi.org/10.1016/j.bmc.2021.116357
- Type
- Article
- Appears in Collections:
- Division of Biomedical Research > Biotherapeutics Translational Research Center > 1. Journal Articles
- Files in This Item:
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