title: Synthesis and evaluation of curcumin derivatives toward an inhibitor of beta-site amyloid precursor protein cleaving enzyme 1.
abstract: To research a new non-peptidyl inhibitor of beta-site amyloid precursor protein cleaving enzyme 1, we focused on the curcumin framework, two phenolic groups combined with an sp2 carbon spacer for low-molecular and high lipophilicity. The structure-activity relationship study of curcumin derivatives is described. Our results indicate that phenolic hydroxy groups and an alkenyl spacer are important structural factors for the inhibition of beta-site amyloid precursor protein cleaving enzyme 1 and, furthermore, non-competitive inhibition of enzyme activity is anticipated from an inhibitory kinetics experiment and docking simulation.
authors.affiliation: Department of Biochemical Engineering, Graduate School of Science and Technology, Yamagata University, Yonezawa, Yamagata 992-8510, Japan. Electronic address: konno@yz.yamagata-u.ac.jp.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Konno
authors.affiliation: Department of Biochemical Engineering, Graduate School of Science and Technology, Yamagata University, Yonezawa, Yamagata 992-8510, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Endo
authors.affiliation: Department of Biochemical Engineering, Graduate School of Science and Technology, Yamagata University, Yonezawa, Yamagata 992-8510, Japan.
authors.forename: Satomi
authors.initials: S
authors.lastname: Ise
authors.affiliation: Department of Biochemical Engineering, Graduate School of Science and Technology, Yamagata University, Yonezawa, Yamagata 992-8510, Japan.
authors.forename: Keiki
authors.initials: K
authors.lastname: Miyazaki
authors.affiliation: Department of Biochemical Engineering, Graduate School of Science and Technology, Yamagata University, Yonezawa, Yamagata 992-8510, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Aoki
authors.affiliation: R&D Center, Protein Wave Co., Nara 631-0006, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Sanjoh
authors.affiliation: Department of Medicinal Chemistry, Kyoto Pharmaceutical University, Yamashina-ku, Kyoto 607-8412, Japan.
authors.forename: Kazuya
authors.initials: K
authors.lastname: Kobayashi
authors.affiliation: Department of Medicinal Chemistry, Kyoto Pharmaceutical University, Yamashina-ku, Kyoto 607-8412, Japan.
authors.forename: Yasunao
authors.initials: Y
authors.lastname: Hattori
authors.affiliation: Department of Medicinal Chemistry, Kyoto Pharmaceutical University, Yamashina-ku, Kyoto 607-8412, Japan. Electronic address: akaji@mb.kyoto-phu.ac.jp.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Akaji
mesh_terms: D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors* / Q000737:chemistry* / Q000378:metabolism; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors* / Q000737:chemistry* / Q000378:metabolism; D003474:Curcumin / Q000138:chemical synthesis* / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human; D003474:Curcumin
keywords: Alzheimer’s disease; BACE1; Curcumin; Structure–activity relationship