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.
Bibliographical noteFunding Information:
This work was supported by the National Research Council of Science & Technology (NST) grant by the Korea government (MSIP) (No. CRC-15-04-KIST ) and KIST institutional program ( 2E26650 ). J.L. was supported by the Sungshin Women's University Research Grant of 2015-2-21-007 .
© 2016 Elsevier Masson SAS
All Science Journal Classification (ASJC) codes
- Drug Discovery
- Organic Chemistry