Design, synthesis and evaluation of diaryl γ-dihydropyrone derivatives as cyclocurcumin mimetics and inhibitors of the aggregation of amyloid β

  • Bioorg Chem. 2020 Nov;104:104302. doi: 10.1016/j.bioorg.2020.104302.
Mayumi Hotsumi  1 ,  Misato Tajiri  1 ,  Koki Makabe  1 ,  Hiroyuki Konno  2
Affiliations
  • 1. Department of Biochemical Engineering, Graduate School of Science and Engineering, Yamagata University, Yonezawa, Yamagata 992-8510, Japan.
  • 2. Department of Biochemical Engineering, Graduate School of Science and Engineering, Yamagata University, Yonezawa, Yamagata 992-8510, Japan. Electronic address: [email protected].
PMID: 33007741 DOI: 10.1016/j.bioorg.2020.104302
Abstract

A structure activity relationship study of cyclocurcumin-derived, diaryl γ-dihydropyrone-based inhibitors of amyloid β aggregation is described. Optimization of the diaryl γ-dihydropyrone framework and two phenolic rings resulted in the identification of diaryl γ-dihydropyrone type cyclocurcumin analogue AY1511, which exhibited potent anti-amyloid β aggregation activity (leading to nanorod-like fragments), sufficient water solubility, and low cytotoxicity.

Keywords
Amyloid β; Amyloid β aggregation; Cyclocurcumin; Diaryl γ-dihydropyrone; Water soluble.
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