2. Academic Validation
  3. Design and synthesis of curcumin derivatives as tau and amyloid β dual aggregation inhibitors

Design and synthesis of curcumin derivatives as tau and amyloid β dual aggregation inhibitors

  • Bioorg Med Chem Lett. 2016 Oct 15;26(20):5024-5028. doi: 10.1016/j.bmcl.2016.08.092.
Michiaki Okuda 1,  Ichiro Hijikuro 2,  Yuki Fujita 3,  Takayuki Teruya 4,  Hirochika Kawakami 4,  Takashi Takahashi 5,  Hachiro Sugimoto 6
Affiliations

Affiliations

  • 1 Graduate School of Brain Science, Doshisha University, 4-1-1 Kizugawadai, Kizugawa, Kyoto 619-0225, Japan; Pharma Eight Co., Ltd., Creation Core Kyoto Mikuruma, 448-5 Kajii-cho, Kamigyo-ku, Kyoto 602-0841, Japan. Electronic address: jt-liaay@mail.doshisha.ac.jp.
  • 2 ChemGenesis Inc., 4-10-2, Nihonbashi-Honcho, Chuo-ku, Tokyo 103-0023, Japan.
  • 3 Graduate School of Brain Science, Doshisha University, 4-1-1 Kizugawadai, Kizugawa, Kyoto 619-0225, Japan; Pharma Eight Co., Ltd., Creation Core Kyoto Mikuruma, 448-5 Kajii-cho, Kamigyo-ku, Kyoto 602-0841, Japan.
  • 4 Pharma Eight Co., Ltd., Creation Core Kyoto Mikuruma, 448-5 Kajii-cho, Kamigyo-ku, Kyoto 602-0841, Japan.
  • 5 Yokohama College of Pharmacy, Natural Product Chemistry & Pharmaceutical Research Center, 601 Matano-cho, Totsuka-ku, Yokohama, Kanagawa 245-0066, Japan.
  • 6 Graduate School of Brain Science, Doshisha University, 4-1-1 Kizugawadai, Kizugawa, Kyoto 619-0225, Japan.
PMID: 27624076 DOI: 10.1016/j.bmcl.2016.08.092
Abstract

Alzheimer's disease (AD) is the most common form of dementia. In an AD patient's brain, senile plaques and neurofibrillary tangles, the abnormal aggregates of amyloid β (Aβ) peptide and Tau Protein, are observed as the two major hallmarks of this disease. To develop a new drug for treatment of AD, we have designed and synthesized a series of curcumin derivatives and evaluated their inhibitory activities against both tau and Aβ aggregation. In this study, we describe the development of the more potent aggregation inhibitor 3-[(1E)-2-(1H-indol-6-yl)ethenyl]-5-[(1E)-2-[2-methoxy-4-(2-pyridylmethoxy) phenyl] ethenyl]-1H-pyrazole (compound 4, PE859). This compound has a better pharmacokinetic profile and pharmacological efficacy in vivo than curcumin, making it suitable as a drug for AD.

Keywords

Aggregation inhibitor; Alzheimer’s disease; Amyloid β; Curcumin; Tau.

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