title: Synthesis and characterization of novel, conjugated, fluorescent DNJ derivatives for α-glucosidase recognition.
abstract: A series of five new fluorescent deoxynojirimycin (DNJ) conjugates were synthesized and evaluated for their inhibitory effect (IC50) on several α- and β-glucosidases. Three of the conjugates showed enhanced activity. The two synthetic conjugates, DNJ-CF31 and DNJ-Me 2, exhibited improved α-glucosidase inhibitory effects compared to DNJ and miglitol. Interestingly, conjugates 1 and 2 showed strong inhibition of almond-derived β-glucosidase, in contrast to the inhibition tendencies of other inhibitors. Conjugate 5 strongly inhibited rat intestinal maltase, even at 0.10μM. A docking study indicated that all five conjugates bind to the active site of α-glucosidase (PDB: 3L4V, derived from Homo sapiens). The DNJ portion of the conjugate fits into the cavity of the enzyme, and the fluorescent part locates randomly on the outside surface. Thus, it is likely that these conjugates can specifically recognize intestinal cells, specifically the α-glucosidase on cell membranes.
authors.affiliation: Department of Chemistry, Shibaura Institute of Technology, 307 Fukasaku, Minuma-ku, Saitama 337-8570, Japan. Electronic address: a-hatano@sic.shibaura-it.ac.jp.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Hatano
authors.affiliation: Department of Chemistry, Shibaura Institute of Technology, 307 Fukasaku, Minuma-ku, Saitama 337-8570, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Kanno
authors.affiliation: Department of Chemistry, Shibaura Institute of Technology, 307 Fukasaku, Minuma-ku, Saitama 337-8570, Japan.
authors.forename: Yuya
authors.initials: Y
authors.lastname: Kondo
authors.affiliation: Department of Chemistry, Shibaura Institute of Technology, 307 Fukasaku, Minuma-ku, Saitama 337-8570, Japan.
authors.forename: Yuta
authors.initials: Y
authors.lastname: Sunaga
authors.affiliation: Department of Chemistry, Shibaura Institute of Technology, 307 Fukasaku, Minuma-ku, Saitama 337-8570, Japan.
authors.forename: Hatsumi
authors.initials: H
authors.lastname: Umezawa
authors.affiliation: Department of Chemistry, Shibaura Institute of Technology, 307 Fukasaku, Minuma-ku, Saitama 337-8570, Japan.
authors.forename: Munehiro
authors.initials: M
authors.lastname: Okada
authors.affiliation: Department of Chemistry, Shibaura Institute of Technology, 307 Fukasaku, Minuma-ku, Saitama 337-8570, Japan.
authors.forename: Hideshi
authors.initials: H
authors.lastname: Yamada
authors.affiliation: Department of Hospital Pharmacy, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.
authors.forename: Ren
authors.initials: R
authors.lastname: Iwaki
authors.affiliation: Department of Hospital Pharmacy, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kato
authors.affiliation: Department of Bioscience and Engineering, Shibaura Institute of Technology, 307 Fukasaku, Minuma-ku, Saitama 337-8570, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Fukui
mesh_terms: D017485:1-Deoxynojirimycin / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005456:Fluorescent Dyes / Q000138:chemical synthesis / Q000737:chemistry*; D005944:Glucosamine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D065089:Glycoside Hydrolase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D000520:alpha-Glucosidases / Q000378:metabolism*
chemical_list: D005456:Fluorescent Dyes; D065089:Glycoside Hydrolase Inhibitors; C501633:deoxynojirimycine; D017485:1-Deoxynojirimycin; D000520:alpha-Glucosidases; D005944:Glucosamine
keywords: DNJ-fluorescent conjugate; Docking simulation; IC(50); Inhibitor; α-Glucosidase