Novel five-membered iminocyclitol derivatives as selective and potent glycosidase inhibitors: new structures for antivirals and osteoarthritis.
A novel 5-membered iminocyclitol derivative was found to be a potent and selective inhibitor of the glycoprotein-processing alpha-glucosidase with a Ki value of 53 nM. This compound was further derivatized to antiviral agents against Japanese encephalitis virus, dengue virus serotype 2 (DEN-2), human SARS coronavirus, and human beta-hexosaminidase (Ki = 2.6 nM), a new target for the development of osteoarthritis therapeutics.
Liang
Pi-Hui
PH
The Genomics Research Center and Institute of Biomedical Sciences, Academia Sinica, No. 128, Academia Road Sec. 2, Nankang District, Taipei, 11529, Taiwan.
Cheng
Wei-Chieh
WC
Lee
Yi-Ling
YL
Yu
Han-Pang
HP
Wu
Ying-Ta
YT
Lin
Yi-Ling
YL
Wong
Chi-Huey
CH
D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D020650:Combinatorial Chemistry Techniques; D003716:Dengue Virus / Q000187:drug effects; D004664:Encephalitis Virus, Japanese / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006026:Glycoside Hydrolases / Q000037:antagonists & inhibitors*; D006573:Heterocyclic Compounds, 1-Ring / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D050112:Imino Pyranoses / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D008954:Models, Biological; D008958:Models, Molecular; D010003:Osteoarthritis / Q000201:enzymology*; D045473:Severe acute respiratory syndrome-related coronavirus / Q000187:drug effects; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D001619:beta-N-Acetylhexosaminidases / Q000037:antagonists & inhibitors
D000998:Antiviral Agents; D004791:Enzyme Inhibitors; D006573:Heterocyclic Compounds, 1-Ring; D050112:Imino Pyranoses; D006026:Glycoside Hydrolases; D001619:beta-N-Acetylhexosaminidases