title: Search for a novel SIRT1 activator: structural modification of SRT1720 and biological evaluation.
abstract: Syntheses and biological evaluation of novel SRT1720 derivatives are described in search for new candidates of SIRT1 activator. Several parts of the SRT1720 structure, including piperazine moiety, quinoxaline ring on the amide group, and position of the amide function, were modified, and the assay results indicated that transfer of the ortho amide-substituent regarding to the imidazo[1,2-b]thiazole core onto the meta position resulted in improvement of SIRT1 activation ability. Modeling analyses of SRT1720 and the most potent derivative bound to model complex of SIRT1 with peptide substrate were also performed.
authors.affiliation: Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan. matsuya@pha.u-toyama.ac.jp
authors.forename: Yuji
authors.initials: Y
authors.lastname: Matsuya
authors.forename: Yuta
authors.initials: Y
authors.lastname: Kobayashi
authors.forename: Sayumi
authors.initials: S
authors.lastname: Uchida
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Itoh
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Sawada
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Suzuki
authors.forename: Naoki
authors.initials: N
authors.lastname: Miyata
authors.forename: Kenji
authors.initials: K
authors.lastname: Sugimoto
authors.forename: Naoki
authors.initials: N
authors.lastname: Toyooka
mesh_terms: D004789:Enzyme Activation / Q000187:drug effects*; D006576:Heterocyclic Compounds, 4 or More Rings / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D062105:Molecular Docking Simulation; D056564:Sirtuin 1 / Q000378:metabolism*; D013844:Thiazoles / Q000737:chemistry / Q000494:pharmacology
chemical_list: D006576:Heterocyclic Compounds, 4 or More Rings; C525422:SRT1720; D013844:Thiazoles; D056564:Sirtuin 1
keywords: Chemical synthesis; Docking study; Structural modification