title: Development of dual targeting inhibitors against aggregations of amyloid-β and tau protein.
abstract: Aggregations of both amyloid-β (Aβ) and hyper-phosphorylated tau proteins are recognized as key pathological manifestations of Alzheimer's disease (AD). Agents that inhibit both those forms of aggregation show promise as drug candidates. Seventeen oligo heteroaromatic compounds were rapidly synthesized via a one-pot, 3- or 4-component coupling procedure. Evaluations showed that compounds E16 and E18 were the most potent inhibitors of Aβ and tau aggregations (E16: IC50s = 0.38, 0.29 μM against Aβ, tau, respectively, E18: IC50s = 0.55, 0.30 μM against Aβ, tau, respectively).
authors.affiliation: Department of Applied Chemistry, Tokyo Institute of Technology, 2-12-1, Ookayama, Meguro-ku, Tokyo 152-8552, Japan. Electronic address: sfuse@apc.titech.ac.jp.
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Fuse
authors.affiliation: Department of Applied Chemistry, Tokyo Institute of Technology, 2-12-1, Ookayama, Meguro-ku, Tokyo 152-8552, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Matsumura
authors.affiliation: Graduate School of Brain Science, Doshisha University, 4-1-1, Kizugawadai, Kizugawa-shi, Kyoto 619-0225, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Fujita
authors.affiliation: Graduate School of Brain Science, Doshisha University, 4-1-1, Kizugawadai, Kizugawa-shi, Kyoto 619-0225, Japan.
authors.forename: Hachiro
authors.initials: H
authors.lastname: Sugimoto
authors.affiliation: Yokohama College of Pharmacy, 601, Matano-cho, Totsuka-ku, Yokohama-shi 245-0066, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Takahashi
mesh_terms: D016229:Amyloid beta-Peptides / Q000737:chemistry*; D004353:Drug Evaluation, Preclinical; D006571:Heterocyclic Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D010446:Peptide Fragments / Q000737:chemistry*; D055503:Protein Multimerization / Q000187:drug effects*; D017433:Protein Structure, Secondary; D016875:tau Proteins / Q000737:chemistry*
chemical_list: D016229:Amyloid beta-Peptides; D006571:Heterocyclic Compounds; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016875:tau Proteins
keywords: Aggregation; Alzheimer's disease; Amyloid-β; Suzuki–Miyaura coupling; Tau