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 language | English |
|---|---|
| Pages (from-to) | 1172-1192 |
| Number of pages | 21 |
| Journal | European Journal of Medicinal Chemistry |
| Volume | 125 |
| DOIs | |
| Publication status | Published - 2017 Jan 1 |
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All Science Journal Classification (ASJC) codes
- Pharmacology
- Drug Discovery
- Organic Chemistry
Cite this
}
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 journal › Article
TY - JOUR
T1 - Discovery of benzimidazole derivatives as modulators of mitochondrial function
T2 - A potential treatment for Alzheimer's disease
AU - Kim, Tae Hun
AU - Yang, Ha Yun
AU - Park, Beoung Gun
AU - Jung, Seo Yun
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
PY - 2017/1/1
Y1 - 2017/1/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84995688336&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84995688336&partnerID=8YFLogxK
U2 - 10.1016/j.ejmech.2016.11.017
DO - 10.1016/j.ejmech.2016.11.017
M3 - Article
C2 - 27855359
AN - SCOPUS:84995688336
VL - 125
SP - 1172
EP - 1192
JO - European Journal of Medicinal Chemistry
JF - European Journal of Medicinal Chemistry
SN - 0223-5234
ER -