title: Virtual ligand screening of α-glucosidase: Identification of a novel potent noncarbohydrate mimetic inhibitor.
abstract: 5-Thiazoleacetamide derivatives of AR122 and AR125 were screened as α-glucosidase inhibitors by in silico high-throughput screening from commercial drug-like small compound libraries. Inhibition of α-glucosidase with AR122 and AR125 is time dependent: with no preincubation, AR122 and AR125 are relatively moderate inhibitors, but interestingly, after a 120 min incubation, they were 50-fold more potent (AR122: IC(50)=2.47 μM and AR125: IC(50)=27.1 μM). Plots of ln [residual α-glucosidase activity %] versus preincubation time show a pseudo-first order kinetics for both inhibitors. Through dialysis of enzyme-inhibitor complexes, no activity recovery was shown. These results suggest that AR122 and AR125 constitute a new class of noncarbohydrate mimetic inhibitor with an irreversible mechanism.
authors.affiliation: Department of Chemistry and Life Science, College of Bioresource Sciences, Nihon University, 1866 Kameino, Fujisawa-shi, Kanagawa 252-0880, Japan. hakamata.wataru@nihon-u.ac.jp
authors.forename: Wataru
authors.initials: W
authors.lastname: Hakamata
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Ishikawa
authors.forename: Yoriko
authors.initials: Y
authors.lastname: Ushijima
authors.forename: Takumi
authors.initials: T
authors.lastname: Tsukagoshi
authors.forename: Saori
authors.initials: S
authors.lastname: Tamura
authors.forename: Takako
authors.initials: T
authors.lastname: Hirano
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Nishio
mesh_terms: D032701:Biomimetics; D002384:Catalysis; D020134:Catalytic Domain; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D004798:Enzymes / Q000737:chemistry; D065089:Glycoside Hydrolase Inhibitors; D020128:Inhibitory Concentration 50; D007700:Kinetics; D008024:Ligands; D008956:Models, Chemical; D012984:Software; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013997:Time Factors; D000520:alpha-Glucosidases / Q000737:chemistry*
chemical_list: D004791:Enzyme Inhibitors; D004798:Enzymes; D065089:Glycoside Hydrolase Inhibitors; D008024:Ligands; D000520:alpha-Glucosidases