title: Dicyanovinyl-substituted J147 analogue inhibits oligomerization and fibrillation of β-amyloid peptides and protects neuronal cells from β-amyloid-induced cytotoxicity.
abstract: A series of novel J147 derivatives were synthesized, and their inhibitory activities against β-amyloid (Aβ) aggregation and toxicity were evaluated by using the oligomer-specific antibody assay, the thioflavin-T fluorescence assay, and a cell viability assay in the transformed SH-SY5Y cell culture. Among the synthesized J147 derivatives, 3j with a 2,2-dicyanovinyl substituent showed the most potent inhibitory activity against Aβ42 oligomerization (IC50 = 17.3 μM) and Aβ42 fibrillization (IC50 = 10.5 μM), and disassembled the preformed Aβ42 fibrils with an EC50 of 10.2 μM. Finally, we confirmed that 3j is also effective at preventing neurotoxicity induced by Aβ42-oligomers as well as Aβ42-fibrils.
authors: Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center, Konkuk University, Hwayang-dong, Gwangjin-gu, Seoul 143-701, Korea. chongy@konkuk.ac.kr.
authors: Kyoungdo
authors: K
authors: Kim
authors: Kwang-su
authors: KS
authors: Park
authors: Mi Kyoung
authors: MK
authors: Kim
authors: Hyunah
authors: H
authors: Choo
authors: Youhoon
authors: Y
authors: Chong
mesh_terms: D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000633:toxicity*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D019610:Cytoprotection / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006834:Hydrazines / Q000737:chemistry / Q000494:pharmacology*; D006845:Hydrocarbons, Fluorinated / Q000737:chemistry / Q000494:pharmacology*; D009474:Neurons / Q000166:cytology* / Q000187:drug effects*; D009570:Nitriles / Q000737:chemistry / Q000494:pharmacology*; D010446:Peptide Fragments / Q000737:chemistry* / Q000633:toxicity*; D055503:Protein Multimerization / Q000187:drug effects*; D017433:Protein Structure, Secondary
chemical_list: C581882:(11C)J147; D016229:Amyloid beta-Peptides; D006834:Hydrazines; D006845:Hydrocarbons, Fluorinated; D009570:Nitriles; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42)