2. Academic Validation
  3. Development of curcumin-based amyloid β aggregation inhibitors for Alzheimer's disease using the SAR matrix approach

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

  • Bioorg Med Chem. 2021 Sep 15:46:116357. doi: 10.1016/j.bmc.2021.116357.
Rohmad Yudi Utomo 1,  Yasunobu Asawa 1,  Satoshi Okada 2,  Hyun Seung Ban 3,  Atsushi Yoshimori 4,  Jürgen Bajorath 5,  Hiroyuki Nakamura 6
Affiliations

Affiliations

  • 1 School of Life Science and Technology, Tokyo Institute of Technology, 4259 Nagatsuta‑cho, Midori‑ku, Yokohama 226‑8501, Japan.
  • 2 School of Life Science and Technology, Tokyo Institute of Technology, 4259 Nagatsuta‑cho, Midori‑ku, Yokohama 226‑8501, Japan; Laboratory for Chemistry and Life Science, Institute of Innovative Research, Tokyo Institute of Technology, 4259 Nagatsuta‑cho, Midori‑ku, Yokohama 226‑8503, Japan.
  • 3 Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141, South Korea.
  • 4 Institute for Theoretical Medicine, Inc., 26‑1, Muraoka‑Higashi 2‑chome, Fujisawa, Kanagawa 251‑0012, Japan.
  • 5 Department of Life Science Informatics, B‑IT, LIMES Program Unit Chemical Biology and Medicinal Chemistry, Rheinische Friedrich-Wilhelms-Universität Friedrich-Hirzebruch-Allee 6, 53115 Bonn, Germany.
  • 6 School of Life Science and Technology, Tokyo Institute of Technology, 4259 Nagatsuta‑cho, Midori‑ku, Yokohama 226‑8501, Japan; Laboratory for Chemistry and Life Science, Institute of Innovative Research, Tokyo Institute of Technology, 4259 Nagatsuta‑cho, Midori‑ku, Yokohama 226‑8503, Japan. Electronic address: hiro@res.titech.ac.jp.
PMID: 34391121 DOI: 10.1016/j.bmc.2021.116357
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.

Keywords

Alzheimer’s disease; Amyloid β; Curcumin; Neurotoxicity; SAR matrix.

Figures
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z