title: A novel competitive class of α-glucosidase inhibitors: (E)-1-phenyl-3-(4-styrylphenyl)urea derivatives.
abstract: Competitive glycosidase inhibitors are generally sugar mimics that are costly and tedious to obtain because they require challenging and elongated chemical synthesis, which must be stereo- and regiocontrolled. Here, we show that readily accessible achiral (E)-1-phenyl-3-(4-strylphenyl)ureas are potent competitive α-glucosidase inhibitors. A systematic synthesis study shows that the 1-phenyl moiety on the urea is critical for ensuring competitive inhibition, and substituents on both terminal phenyl groups contribute to inhibition potency. The most potent inhibitor, compound 12 (IC(50)=8.4 μM, K(i)=3.2 μM), manifested a simple slow-binding inhibition profile for α-glucosidase with the kinetic parameters k(3)=0.005256 μM(-1) min(-1), k(4)=0.003024 min(-1), and K(i)(app) =0.5753 μM.
authors.affiliation: Division of Applied Life Science, Gyeongsang National University, Jinju, South Korea.
authors.forename: Jun Young
authors.initials: JY
authors.lastname: Kim
authors.forename: Ji Won
authors.initials: JW
authors.lastname: Lee
authors.forename: Young Soo
authors.initials: YS
authors.lastname: Kim
authors.forename: Yuno
authors.initials: Y
authors.lastname: Lee
authors.forename: Young Bae
authors.initials: YB
authors.lastname: Ryu
authors.forename: Songmi
authors.initials: S
authors.lastname: Kim
authors.forename: Hyung Won
authors.initials: HW
authors.lastname: Ryu
authors.forename: Marcus J
authors.initials: MJ
authors.lastname: Curtis-Long
authors.forename: Keun Woo
authors.initials: KW
authors.lastname: Lee
authors.forename: Woo Song
authors.initials: WS
authors.lastname: Lee
authors.forename: Ki Hun
authors.initials: KH
authors.lastname: Park
mesh_terms: D001667:Binding, Competitive; D004791:Enzyme Inhibitors / Q000737:chemistry*; D065089:Glycoside Hydrolase Inhibitors; D007700:Kinetics; D010671:Phenylurea Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D012441:Saccharomyces cerevisiae / Q000201:enzymology; D013329:Structure-Activity Relationship; D014508:Urea / Q000031:analogs & derivatives* / Q000737:chemistry; D000520:alpha-Glucosidases / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D065089:Glycoside Hydrolase Inhibitors; D010671:Phenylurea Compounds; D014508:Urea; D000520:alpha-Glucosidases