title: β-secretase inhibitory activity of phenolic acid conjugated chitooligosaccharides.
abstract: Eight kinds of phenolic acid conjugated chitooligosaccharides (COSs) were synthesized using hydroxyl benzoic acid and hydroxyl cinnamic acid. These phenolic acid conjugated-COSs with different substitution groups, including p-hydroxyl, 3,4-dihydroxyl, 3-methoxyl-4-hydroxyl and 3,5-dimethoxyl-4-hydroxy groups, were evaluated for their inhibitory activities against β-site amyloid precursor protein (APP)-cleaving enzyme (BACE) and inhibited BACE with a ratio of 50.8%, 74.8%, 62.1%, 64.8% and 42.6%, respectively at the concentration of 1,000 μg/mL. BACE is a critical component to reduce the levels of Aβ amyloid peptide in Alzheimer's disease (AD) which is based on the amyloid cascade theory in the brain, as this protease initiates the first step in Aβ production. Among them, Caffeic acid conjugated-COS (CFA-COS) was further analysed to determine mode of inhibition of BACE and it showed non-competitive inhibition. Hence in this study, we suggest that CFA-COS derivatives have potential to be used as novel BACE inhibitors to reduce the risk of AD.
authors.affiliation: Hongcheon Institute of Medicinal Herb, 101 Yeonbong-ri, hheon-eup, Hongcheon, Gangwondo, Republic of Korea.
authors.forename: Tae-Kil
authors.initials: TK
authors.lastname: Eom
authors.forename: Bomi
authors.initials: B
authors.lastname: Ryu
authors.forename: Jung-Kwon
authors.initials: JK
authors.lastname: Lee
authors.forename: Hee-Guk
authors.initials: HG
authors.lastname: Byun
authors.forename: Sun-Joo
authors.initials: SJ
authors.lastname: Park
authors.forename: Se-Kwon
authors.initials: SK
authors.lastname: Kim
mesh_terms: D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors*; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors*; D002109:Caffeic Acids / Q000737:chemistry; D060326:Chemistry Techniques, Synthetic; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D062385:Hydroxybenzoates / Q000737:chemistry*; D020128:Inhibitory Concentration 50; D009844:Oligosaccharides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D002109:Caffeic Acids; D004791:Enzyme Inhibitors; D062385:Hydroxybenzoates; D009844:Oligosaccharides; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human; C017616:phenolic acid; C040048:caffeic acid