Development of curcumin-based amyloid β aggregation inhibitors for Alzheimer's disease using the SAR matrix approach

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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
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