Discovery of benzimidazole derivatives as modulators of mitochondrial function: A potential treatment for Alzheimer's disease

  • Kim, TaeHun
  • Yang, Ha Yun
  • Park, Beoung Gun
  • Jung, Seo Yun
  • Park, Jong-Hyun
  • ... Min, Sun-Joon
  • 외 9명
Citations

WEB OF SCIENCE

37
Citations

SCOPUS

40

초록

In this study, we designed a library of compounds based on the structures of well-known ligands of the 18 kDa translocator protein (TSPO), one of the putative components of the mPTP. We performed diverse mitochondrial functional assays to assess their ability to restore cells from A beta-induced toxicity in vitro and in vivo. Among tested compounds, compound 25 effectively improved cognitive function in animal models of AD. Given the excellent in vitro and in vivo activity and a favorable pharmacokinetic profile of compound 25, we believe that it can serve as a promising lead compound for a potential treatment option for AD. (C) 2016 Elsevier Masson SAS. All rights reserved.

키워드

Translocator proteinTSPOMitochondrial permeability transition poreAlzheimer's diseaseMitochondrial dysfunctionA betaPERMEABILITY TRANSITION POREAMYLOID-BETACYCLOPHILIN-DA-BETAINHIBITORTSPOREPERFUSIONDYSFUNCTIONHYPOTHESISDIAGNOSIS
제목
Discovery of benzimidazole derivatives as modulators of mitochondrial function: A potential treatment for Alzheimer's disease
저자
Kim, TaeHunYang, Ha YunPark, Beoung GunJung, Seo YunPark, Jong-HyunPark, Ki DukMin, Sun-JoonTae, JinsungYang, HyejinCho, SuengmokCho, Sung JinSong, HyundongMook-Jung, InheeLee, JiyounPae, Ae Nim
DOI
10.1016/j.ejmech.2016.11.017
발행일
2017-01
유형
Article
저널명
European Journal of Medicinal Chemistry
125
페이지
1172 ~ 1192