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2017 - Discovery of benzimidazole derivatives as modulators of mitochondrial function: A potential treatment for Alzheimer's disease

icon pl  Patchliner publication in PLoS ONE (2017)

Authors: 
Kim T., Yang H.Y., Park B.G., Jung S.Y., Park J.H., Park K.D., Min S.J., Tae J., Yang H., Cho S., Cho S.J., Song H., Mook-Jung I., Lee J., Pae A.N.

 

Journal: 
Eur J Med Chem (2017) 125:1172-1192


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.

Highlights:

- Benzimidazole derivatives were synthesized as mitochondrial functional modulators.
- Mitochondrial functional assays were performed to assess their restoring ability.
- Lead compound 25 effectively improved cognitive function in AD animal models.


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