title: Design, synthesis and biological evaluation of bicyclic iminosugar hybrids: conformational constraint as an effective tool for tailoring the selectivity of α-glucosidase inhibitors.
abstract: Principle guided design of glycan processing enzyme inhibitors involves embedding aromatic groups onto charge and shape mimics. Intramolecular azide-alkyne cycloaddition was used as a simple and versatile strategy for the synthesis of novel condensed bicyclic triazoles from carbohydrate derived Perlin aldehydes. These newly synthesised molecules were evaluated for glycosidase inhibition against 11 commercially available enzymes and were found to possess significant affinity (micromolar range) as well as high degree of selectivity for α-glucosidases. Conformational restriction was identified as an important tool to customize the selectivity of enzyme inhibition by five-membered iminosugars.
authors: Division of Medicinal and Process Chemistry, CSIR-Central Drug Research Institute, BS-10/1, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow 226031, India. akshaw55@yahoo.com.
authors: Inderpreet
authors: I
authors: Arora
authors: Vivek Kr
authors: VK
authors: Kashyap
authors: Alok Kumar
authors: AK
authors: Singh
authors: Arunava
authors: A
authors: Dasgupta
authors: Brijesh
authors: B
authors: Kumar
authors: Arun K
authors: AK
authors: Shaw
mesh_terms: D000470:Alkaloids / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000737:chemistry*; D065089:Glycoside Hydrolase Inhibitors / Q000737:chemistry*; D006801:Humans; D007004:Hypoglycemic Agents / Q000737:chemistry; D050111:Imino Sugars / Q000737:chemistry; D020128:Inhibitory Concentration 50; D007700:Kinetics; D008968:Molecular Conformation; D015394:Molecular Structure; D012275:Oryza / Q000201:enzymology; D011485:Protein Binding; D014230:Triazoles / Q000737:chemistry; D000520:alpha-Glucosidases / Q000737:chemistry*
chemical_list: D000470:Alkaloids; D004791:Enzyme Inhibitors; D065089:Glycoside Hydrolase Inhibitors; D007004:Hypoglycemic Agents; D050111:Imino Sugars; D014230:Triazoles; D000520:alpha-Glucosidases