title: Toward potent α-glucosidase inhibitors based on xanthones: a closer look into the structure-activity correlations.
abstract: A series of novel xanthone derivatives 6-16 having non-coplanar and flexible structures were synthesized as potent α-glucosidase inhibitors. Biological evaluation indicated that compounds 6-12 bearing one or two naphthol moieties exhibited up to 30-fold enhanced activities compared with their corresponding parent compounds 2-5, whereas compounds 13-16 bearing one dihydroxylnaphthalenyl group showed decreased activities compared with their corresponding analogs 6-9 having one naphthol group. Among them, compounds 7-8, 10-12 and 15 were more active than 1-deoxynojirimycin, a well-known inhibitor for α-glucosidase. The structure-activity correlations suggested that inhibiting of α-glucosidase was a result of multiple interactions with the enzyme, including π-stacking, hydrophobic effect and conformational flexibility due to the structural non-coplanarity. In addition, compounds 4, 8 and 15 showed non-competitive inhibition.
authors.affiliation: School of Chemistry & Chemical Engineering, Sun Yat-Sen University, Guangzhou 510275, PR China.
authors.forename: Gai-Li
authors.initials: GL
authors.lastname: Li
authors.forename: Jia-Yun
authors.initials: JY
authors.lastname: He
authors.forename: Aiqin
authors.initials: A
authors.lastname: Zhang
authors.forename: Yiqian
authors.initials: Y
authors.lastname: Wan
authors.forename: Bo
authors.initials: B
authors.lastname: Wang
authors.forename: Wen-Hua
authors.initials: WH
authors.lastname: Chen
mesh_terms: D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D065089:Glycoside Hydrolase Inhibitors; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D021241:Spectrometry, Mass, Electrospray Ionization; D013329:Structure-Activity Relationship; D044004:Xanthones / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D065089:Glycoside Hydrolase Inhibitors; D044004:Xanthones