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

Tae Hun Kim, Ha Yun Yang, Beoung Gun Park, Seo Yun Jung, Jong Hyun Park, Ki Duk Park, Sun Joon Min, Jinsung Tae, Hyejin Yang, Suengmok Cho, Sung Jin Cho, Hyundong Song, Inhee Mook-Jung, Jiyoun Lee, Ae Nim Pae

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

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 Aβ-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.

Original languageEnglish
Pages (from-to)1172-1192
Number of pages21
JournalEuropean Journal of Medicinal Chemistry
Volume125
DOIs
Publication statusPublished - 2017 Jan 1

Fingerprint

Lead compounds
Pharmacokinetics
Modulators
Toxicity
Assays
Alzheimer Disease
Animals
Ligands
Derivatives
Aptitude
Cognition
Proteins
Animal Models
benzimidazole
In Vitro Techniques
Lead

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

Cite this

Kim, Tae Hun ; Yang, Ha Yun ; Park, Beoung Gun ; Jung, Seo Yun ; Park, Jong Hyun ; Park, Ki Duk ; Min, Sun Joon ; Tae, Jinsung ; Yang, Hyejin ; Cho, Suengmok ; Cho, Sung Jin ; Song, Hyundong ; Mook-Jung, Inhee ; Lee, Jiyoun ; Pae, Ae Nim. / Discovery of benzimidazole derivatives as modulators of mitochondrial function : A potential treatment for Alzheimer's disease. In: European Journal of Medicinal Chemistry. 2017 ; Vol. 125. pp. 1172-1192.
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Kim, TH, Yang, HY, Park, BG, Jung, SY, Park, JH, Park, KD, Min, SJ, Tae, J, Yang, H, Cho, S, Cho, SJ, Song, H, Mook-Jung, I, Lee, J & Pae, AN 2017, 'Discovery of benzimidazole derivatives as modulators of mitochondrial function: A potential treatment for Alzheimer's disease', European Journal of Medicinal Chemistry, vol. 125, pp. 1172-1192. https://doi.org/10.1016/j.ejmech.2016.11.017

Discovery of benzimidazole derivatives as modulators of mitochondrial function : A potential treatment for Alzheimer's disease. / Kim, Tae Hun; Yang, Ha Yun; Park, Beoung Gun; Jung, Seo Yun; Park, Jong Hyun; Park, Ki Duk; Min, Sun Joon; Tae, Jinsung; Yang, Hyejin; Cho, Suengmok; Cho, Sung Jin; Song, Hyundong; Mook-Jung, Inhee; Lee, Jiyoun; Pae, Ae Nim.

In: European Journal of Medicinal Chemistry, Vol. 125, 01.01.2017, p. 1172-1192.

Research output: Contribution to journalArticle

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AU - Park, Jong Hyun

AU - Park, Ki Duk

AU - Min, Sun Joon

AU - Tae, Jinsung

AU - Yang, Hyejin

AU - Cho, Suengmok

AU - Cho, Sung Jin

AU - Song, Hyundong

AU - Mook-Jung, Inhee

AU - Lee, Jiyoun

AU - Pae, Ae Nim

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