Development of curcumin-based amyloid β aggregation inhibitors for Alzheimer's disease using the SAR matrix approach.
Basic Information
ID: ALA4808231
Journal: Bioorg Med Chem
Title: Development of curcumin-based amyloid β aggregation inhibitors for Alzheimer's disease using the SAR matrix approach.
Authors: Yudi Utomo R, Asawa Y, Okada S, Ban HS, Yoshimori A, Bajorath J, Nakamura H.
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.
CiteXplore: 34391121
DOI: 10.1016/j.bmc.2021.116357
Patent ID: ┄