title: Inhibitory effect of flavonoids on human glutaminyl cyclase.
abstract: Glutaminyl cyclase (QC) plays an important role in the pathogenesis of Alzheimer's disease (AD) and can be a potential target for the development of novel anti-AD agents. However, the study of QC inhibitors are still less. Here, phenol-4' (R1-), C5-OH (R2-) and C7-OH (R3-) modified apigenin derivatives were synthesized as a new class of human QC (hQC) inhibitors. The efficacy investigation of these compounds was performed by spectrophotometric assessment and the structure-activity relationship (SAR) was evaluated. Molecular docking was also carried out to analyze the binding mode of the synthesized flavonoid to the active site of hQC.
authors.affiliation: College of Life Sciences, Shenzhen University, Shenzhen 518060, China; Department of Pharmacy, School of Medicine, Shenzhen University, No. 3688, Nanhai Road, Nanshan, Shenzhen 518060, China.
authors.forename: Manman
authors.initials: M
authors.lastname: Li
authors.affiliation: College of Life Sciences, Shenzhen University, Shenzhen 518060, China; Department of Pharmacy, School of Medicine, Shenzhen University, No. 3688, Nanhai Road, Nanshan, Shenzhen 518060, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Dong
authors.affiliation: College of Life Sciences, Shenzhen University, Shenzhen 518060, China; Department of Pharmacy, School of Medicine, Shenzhen University, No. 3688, Nanhai Road, Nanshan, Shenzhen 518060, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Yu
authors.affiliation: College of Life Sciences, Shenzhen University, Shenzhen 518060, China.
authors.forename: Yongdong
authors.initials: Y
authors.lastname: Zou
authors.affiliation: College of Life Sciences, Shenzhen University, Shenzhen 518060, China.
authors.forename: Yizhi
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: School of Pharmaceutical Science, Sun Yat-sen University, Guangzhou 510006, China.
authors.forename: Xianzhang
authors.initials: X
authors.lastname: Bu
authors.affiliation: Key Laboratory of Structural Biology, School of Chemical Biology & Biotechnology, Peking University, Shenzhen Graduate School, Shenzhen 518055, China.
authors.forename: Junmin
authors.initials: J
authors.lastname: Quan
authors.affiliation: Department of Pharmacy, School of Medicine, Shenzhen University, No. 3688, Nanhai Road, Nanshan, Shenzhen 518060, China.
authors.forename: Zhendan
authors.initials: Z
authors.lastname: He
authors.affiliation: College of Life Sciences, Shenzhen University, Shenzhen 518060, China; Department of Pharmacy, School of Medicine, Shenzhen University, No. 3688, Nanhai Road, Nanshan, Shenzhen 518060, China. Electronic address: wuhq@szu.edu.cn.
authors.forename: Haiqiang
authors.initials: H
authors.lastname: Wu
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy / Q000201:enzymology; D019881:Aminoacyltransferases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D005419:Flavonoids / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D062105:Molecular Docking Simulation; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D005419:Flavonoids; D019881:Aminoacyltransferases; C059280:glutaminyl-peptide cyclotransferase
keywords: Alzheimer’s disease; Enzyme inhibitor; Flavonoids; Glutaminyl cyclase; Synthesis