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.
authors.affiliation: Convergence Research Center for Diagnosis, Treatment and Care System of Dementia, Korea Institute of Science and Technology, PO Box 131, Cheongryang, Seoul 130-650, Republic of Korea; Biological Chemistry, Korea University of Science and Technology, Yuseong-Gu, Daejon 305-350, Republic of Korea.
authors.forename: TaeHun
authors.initials: T
authors.lastname: Kim
authors.affiliation: Convergence Research Center for Diagnosis, Treatment and Care System of Dementia, Korea Institute of Science and Technology, PO Box 131, Cheongryang, Seoul 130-650, Republic of Korea; Department of Chemistry, Yonsei University, Seodaemun-gu, Seoul 120-749, Republic of Korea.
authors.forename: Ha Yun
authors.initials: HY
authors.lastname: Yang
authors.affiliation: Convergence Research Center for Diagnosis, Treatment and Care System of Dementia, Korea Institute of Science and Technology, PO Box 131, Cheongryang, Seoul 130-650, Republic of Korea.
authors.forename: Beoung Gun
authors.initials: BG
authors.lastname: Park
authors.affiliation: Convergence Research Center for Diagnosis, Treatment and Care System of Dementia, Korea Institute of Science and Technology, PO Box 131, Cheongryang, Seoul 130-650, Republic of Korea.
authors.forename: Seo Yun
authors.initials: SY
authors.lastname: Jung
authors.affiliation: Convergence Research Center for Diagnosis, Treatment and Care System of Dementia, Korea Institute of Science and Technology, PO Box 131, Cheongryang, Seoul 130-650, Republic of Korea.
authors.forename: Jong-Hyun
authors.initials: JH
authors.lastname: Park
authors.affiliation: Convergence Research Center for Diagnosis, Treatment and Care System of Dementia, Korea Institute of Science and Technology, PO Box 131, Cheongryang, Seoul 130-650, Republic of Korea; Biological Chemistry, Korea University of Science and Technology, Yuseong-Gu, Daejon 305-350, Republic of Korea.
authors.forename: Ki Duk
authors.initials: KD
authors.lastname: Park
authors.affiliation: Department of Applied Chemistry, Hanyang University, Ansan, Gyeonggi-do 15888, Republic of Korea.
authors.forename: Sun-Joon
authors.initials: SJ
authors.lastname: Min
authors.affiliation: Department of Chemistry, Yonsei University, Seodaemun-gu, Seoul 120-749, Republic of Korea.
authors.forename: Jinsung
authors.initials: J
authors.lastname: Tae
authors.affiliation: Korea Food Research Institute, Sungnam 463-746, Republic of Korea.
authors.forename: Hyejin
authors.initials: H
authors.lastname: Yang
authors.affiliation: Korea Food Research Institute, Sungnam 463-746, Republic of Korea.
authors.forename: Suengmok
authors.initials: S
authors.lastname: Cho
authors.affiliation: New Drug Development Center, Daegu-Gyeongbuk Medical Innovation Foundation, Daegu, Republic of Korea.
authors.forename: Sung Jin
authors.initials: SJ
authors.lastname: Cho
authors.affiliation: Department of Biochemistry and Biomedical Sciences, College of Medicine, Seoul National University, 103 Daehak-ro, Seoul 110-799, Jongno-gu, Republic of Korea.
authors.forename: Hyundong
authors.initials: H
authors.lastname: Song
authors.affiliation: Department of Biochemistry and Biomedical Sciences, College of Medicine, Seoul National University, 103 Daehak-ro, Seoul 110-799, Jongno-gu, Republic of Korea.
authors.forename: Inhee
authors.initials: I
authors.lastname: Mook-Jung
authors.affiliation: Department of Global Medical Science, Sungshin University, Seoul 142-732, Republic of Korea. Electronic address: jlee@sungshin.ac.kr.
authors.forename: Jiyoun
authors.initials: J
authors.lastname: Lee
authors.affiliation: Convergence Research Center for Diagnosis, Treatment and Care System of Dementia, Korea Institute of Science and Technology, PO Box 131, Cheongryang, Seoul 130-650, Republic of Korea; Biological Chemistry, Korea University of Science and Technology, Yuseong-Gu, Daejon 305-350, Republic of Korea. Electronic address: anpae@kist.re.kr.
authors.forename: Ae Nim
authors.initials: AN
authors.lastname: Pae
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D001562:Benzimidazoles / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D003071:Cognition / Q000187:drug effects; D006801:Humans; D008024:Ligands; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D008822:Mice, Transgenic; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism; D000083162:Mitochondrial Permeability Transition Pore; D008958:Models, Molecular; D017207:Rats, Sprague-Dawley; D018079:Receptors, GABA / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D001562:Benzimidazoles; D008024:Ligands; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D018079:Receptors, GABA; C499229:TSPO protein, human
keywords: Alzheimer's disease; Aβ; Mitochondrial dysfunction; Mitochondrial permeability transition pore; TSPO; Translocator protein