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

doi:10.1016/j.ejmech.2016.11.017

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

Department of Chemistry

Research output: Contribution to journal › Article › peer-review

25 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 language	English
Pages (from-to)	1172-1192
Number of pages	21
Journal	European Journal of Medicinal Chemistry
Volume	125
DOIs	https://doi.org/10.1016/j.ejmech.2016.11.017
Publication status	Published - 2017

Bibliographical note

Funding 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 .

Publisher Copyright:
© 2016 Elsevier Masson SAS

All Science Journal Classification (ASJC) codes

Pharmacology
Drug Discovery
Organic Chemistry

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10.1016/j.ejmech.2016.11.017

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Kim, T. H., 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. (2017). Discovery of benzimidazole derivatives as modulators of mitochondrial function: A potential treatment for Alzheimer's disease. European Journal of Medicinal Chemistry, 125, 1172-1192. https://doi.org/10.1016/j.ejmech.2016.11.017

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

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.",

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

note = "Funding 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 . Publisher Copyright: {\textcopyright} 2016 Elsevier Masson SAS",

year = "2017",

doi = "10.1016/j.ejmech.2016.11.017",

language = "English",

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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, 2017, p. 1172-1192.

Research output: Contribution to journal › Article › peer-review

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

N1 - Funding 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 . Publisher Copyright: © 2016 Elsevier Masson SAS

PY - 2017

Y1 - 2017

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.

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JO - CHIM.THER.

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SN - 0223-5234

ER -

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

Abstract

Bibliographical note

All Science Journal Classification (ASJC) codes

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