title: Synthesis, conformational study, glycosidase inhibitory activity and molecular docking studies of dihydroxylated 4- and 5-amino-iminosugars.
abstract: An efficient methodology for the synthesis of new amino iminosugars 6a, 7a and 8, starting from D-glucose, is reported. The conformational study using (1)H NMR data showed that the amino iminosugar 6a exists in the (2)C5 while; the 7a and 8 exist in the (5)C2 conformation. The inhibition activities with different glycosidases showed that 6a and 7a are poor glycosidase inhibitors. However, amino iminosugar 8 showed selective inhibition against the β-galactosidase (IC50 = 43 μM, Ki = 153 μM). These results are substantiated by the molecular docking studies.
authors.affiliation: Department of Chemistry, Garware Research Centre, Savitribai Phule Pune University (formerly University of Pune), Pune 411007, India.
authors.forename: Vijay M
authors.initials: VM
authors.lastname: Kasture
authors.affiliation: Department of Chemistry, Garware Research Centre, Savitribai Phule Pune University (formerly University of Pune), Pune 411007, India.
authors.forename: Navnath B
authors.initials: NB
authors.lastname: Kalamkar
authors.affiliation: Division of Biochemistry, Department of Chemistry, Savitribai Phule Pune University (formerly University of Pune), Pune 411007, India.
authors.forename: Roopa J
authors.initials: RJ
authors.lastname: Nair
authors.affiliation: Institute of Bioinformatics and Biotechnology, Savitribai Phule Pune University (formerly University of Pune), Pune 411007, India.
authors.forename: Rakesh S
authors.initials: RS
authors.lastname: Joshi
authors.affiliation: Division of Biochemistry, Department of Chemistry, Savitribai Phule Pune University (formerly University of Pune), Pune 411007, India.
authors.forename: Sushma G
authors.initials: SG
authors.lastname: Sabharwal
authors.affiliation: Department of Chemistry, Garware Research Centre, Savitribai Phule Pune University (formerly University of Pune), Pune 411007, India. Electronic address: ddd@chem.unipune.ac.in.
authors.forename: Dilip D
authors.initials: DD
authors.lastname: Dhavale
mesh_terms: D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D065089:Glycoside Hydrolase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D050111:Imino Sugars / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D001616:beta-Galactosidase / Q000037:antagonists & inhibitors*
chemical_list: D065089:Glycoside Hydrolase Inhibitors; D050111:Imino Sugars; D001616:beta-Galactosidase
keywords: Amino piperidine; Chiron approach; Glycosidase inhibitor; Iminosugar; Molecular docking; Reductive amino-cyclization