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Eur J Med Chem. 2017 Sep 29;138:1066-1075. doi: 10.1016/j.ejmech.2017.07.026. Epub 2017 Jul 18.

Structure-activity relations of rosmarinic acid derivatives for the amyloid β aggregation inhibition and antioxidant properties.

Author information

1
Division of Sustainable and Environmental Engineering, Graduate School of Engineering, Muroran Institute of Technology, 27-1 Mizumoto, Muroran 050-8585, Japan.
2
Tohoku Medical and Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan.
3
Division of Sustainable and Environmental Engineering, Graduate School of Engineering, Muroran Institute of Technology, 27-1 Mizumoto, Muroran 050-8585, Japan. Electronic address: uwai@mmm.muroran-it.ac.jp.

Abstract

Amyloid-β aggregation inhibitors are expected to be therapeutic or prophylactic agents for Alzheimer's disease. Rosmarinic acid, which is one of the main aggregation inhibitors derived from Lamiaceae, was employed as a lead compound and its 25 derivatives were synthesized. In this study, the structure-activity relations of rosmarinic acid derivatives for the amyloid-β aggregation inhibitory effect (MSHTS assay), antioxidant properties, and xanthine oxidase inhibition were evaluated. Among the tested compounds, compounds 16d and 19 were found to the most potent amyloid aggregation inhibitors. The SAR revealed that the necessity of the presence of the phenolic hydroxyl on one side of the molecule as well as the lipophilicity of the entire molecule. The importance of these structural properties was also supported by docking simulations.

KEYWORDS:

Aggregation; Alzheimer's disease; Amyloid-beta; Inhibitor; Rosmarinic acid; Structure–activity relationship

PMID:
28759879
DOI:
10.1016/j.ejmech.2017.07.026
[Indexed for MEDLINE]

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