title: 'Click chemistry' synthesis of 1-(α-D-mannopyranosyl)-1,2,3-triazoles for inhibition of α-mannosidases.
abstract: Three new triazole conjugates derived from d-mannose were synthesized and assayed in in vitro assays to investigate their ability to inhibit α-mannosidase enzymes from the glycoside hydrolase (GH) families 38 and 47. The triazole conjugates were more selective for a GH47 α-mannosidase (Aspergillus saitoi α1,2-mannosidase), showing inhibition at the micromolar level (IC50 values of 50-250 μM), and less potent towards GH38 mannosidases (IC50 values in the range of 0.5-6 mM towards jack bean α-mannosidase or Drosophila melanogaster lysosomal and Golgi α-mannosidases). The highest selectivity ratio [IC50(GH38)/IC50(GH47)] of 100 was exhibited by the phenyltriazole conjugate. To understand structure-activity properties of synthesized compounds, 3-D complexes of inhibitors with α-mannosidases were built using molecular docking calculations.
authors: Institute of Chemistry, Center for Glycomics, Slovak Academy of Sciences, Dúbravska cesta 9, 845 38 Bratislava, Slovakia. Electronic address: Monika.Polakova@savba.sk.
authors: Monika
authors: M
authors: Poláková
authors: Department für Chemie, Universität für Bodenkultur, A-1190 Wien, Austria.
authors: Rhiannon
authors: R
authors: Stanton
authors: Department für Chemie, Universität für Bodenkultur, A-1190 Wien, Austria.
authors: Iain B H
authors: IB
authors: Wilson
authors: Department of Cellular and Molecular Biology of Drugs, Faculty of Pharmacy, Comenius University, Kalinčiakova 8, 832 32 Bratislava, Slovakia.
authors: Ivana
authors: I
authors: Holková
authors: Institute of Chemistry, Center for Glycomics, Slovak Academy of Sciences, Dúbravska cesta 9, 845 38 Bratislava, Slovakia.
authors: Sergej
authors: S
authors: Šesták
authors: Institute of Chemistry, Center for Glycomics, Slovak Academy of Sciences, Dúbravska cesta 9, 845 38 Bratislava, Slovakia.
authors: Eva
authors: E
authors: Machová
authors: Institute of Chemistry, Center for Glycomics, Slovak Academy of Sciences, Dúbravska cesta 9, 845 38 Bratislava, Slovakia; Department of Cellular and Molecular Biology of Drugs, Faculty of Pharmacy, Comenius University, Kalinčiakova 8, 832 32 Bratislava, Slovakia.
authors: Zuzana
authors: Z
authors: Jandová
authors: Institute of Chemistry, Center for Glycomics, Slovak Academy of Sciences, Dúbravska cesta 9, 845 38 Bratislava, Slovakia.
authors: Juraj
authors: J
authors: Kóňa
mesh_terms: D000818:Animals; D020134:Catalytic Domain; D057930:Click Chemistry; D004791:Enzyme Inhibitors / Q000138:chemical synthesis*; D006801:Humans; D008958:Models, Molecular; D011485:Protein Binding; D014230:Triazoles / Q000138:chemical synthesis*; D043323:alpha-Mannosidase / Q000037:antagonists & inhibitors / Q000737:chemistry*
chemical_list: D004791:Enzyme Inhibitors; D014230:Triazoles; D043323:alpha-Mannosidase
keywords: 1-(d-Mannopyranosyl)-1,2,3-triazole; Click reaction; Glycoside hydrolase; Molecular docking; α-Mannosidase inhibitor