Synthesis, computational study and glycosidase inhibitory activity of polyhydroxylated conidine alkaloids--a bicyclic iminosugar.
New bicyclic conidine iminosugars 1d and 1e were synthesized from D-glucose. Thus, D-glucose was converted to sugar beta-amino acids 3a and 3b in good yields. Individual treatment of 3a/3b with the Mukaiyama reagent afforded sugar beta-lactams 4a/4b that on reduction with LiAlH(4)/AlCl(3) gave azetidines 5a/5b with a sugar appendage. Reductive aminocyclization of sugar azetidines 5a/5b afforded the corresponding conidine iminosugars 1d/1e. Based on the (1)H NMR and DFT calculation studies the conformation of 1d was assigned as half chair A2 and that of 1e as a boat B2. The glycosidase inhibitory activities of 1d and 1e such as alpha-mannosidase, alpha-glucosidase and alpha-galactosidase were studied. The alpha-amylase activity was compared with acarbose. Compound 1d was found to be a moderate inhibitor of glycosidases while 1e was noticed to be a good inhibitor of alpha-mannosidase and a moderate inhibitor of other glycosidases. These results were substantiated by molecular docking studies using WHAT IF software and the AUTODOCK 3.0 program.
Sanap
Shrihari P
SP
Garware Research Centre, Department of Chemistry, University of Pune, Pune-411007, India.
Ghosh
Sougata
S
Jabgunde
Amit M
AM
Pinjari
Rahul V
RV
Gejji
Shridhar P
SP
Singh
Shailza
S
Chopade
Balu A
BA
Dhavale
Dilip D
DD
D000470:Alkaloids / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D003198:Computer Simulation; D019277:Entropy; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D006026:Glycoside Hydrolases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006900:Hydroxylation; D050111:Imino Sugars / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D008968:Molecular Conformation; D011108:Polymers / Q000737:chemistry*; D011789:Quantum Theory
D000470:Alkaloids; D004791:Enzyme Inhibitors; D050111:Imino Sugars; D011108:Polymers; C039164:conidine; D006026:Glycoside Hydrolases