Unsaturated N-acetyl- D-glucosaminuronic acid glycosides as inhibitors of influenza virus sialidase.
The threat of pandemic influenza is a significant concern of governments worldwide. There is a very limited and relatively expensive armament to tackle such a pandemic should it occur. This fact provides much impetus to the scientific community for the discovery of new and less expensive anti-influenza drugs. Our longstanding interest in the inhibition of influenza virus sialidase, coupled with the development of simple carbohydrates that mimic an unsaturated derivative of the enzyme's naturally-occurring ligand, N-acetylneuraminic acid, has led us to investigate the development of influenza virus sialidase inhibitors based on these mimetics. We have successfully prepared a range of these compounds, in good yield, from the relatively inexpensive carbohydrate N-acetylglucosamine utilising a short synthetic procedure. We have employed a sialidase inhibition assay for biological evaluation of the target compounds and to our delight these mimetics have displayed significant inhibition of influenza virus sialidase.
Institute for Glycomics, Griffith University, Gold Coast Campus, PMB 50 Gold Coast Mail Centre, Queensland 9726, Australia.
Maretta C
MC
Mann
Tasneem
T
Islam
Jeffrey C
JC
Dyason
Pas
P
Florio
Carolyn J
CJ
Trower
Robin J
RJ
Thomson
Mark
M
von Itzstein
D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D006027:Glycosides / Q000737:chemistry*; D008958:Models, Molecular; D018716:Molecular Mimicry; D009439:Neuraminidase / Q000037:antagonists & inhibitors* / Q000737:chemistry; D011487:Protein Conformation; D014574:Uronic Acids / Q000737:chemistry*
D004791:Enzyme Inhibitors; D006027:Glycosides; D014574:Uronic Acids; C000156:N-acetylglucosaminuronic acid; D009439:Neuraminidase