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.
Mann
Maretta C
MC
Institute for Glycomics, Griffith University, Gold Coast Campus, PMB 50 Gold Coast Mail Centre, Queensland 9726, Australia.
Islam
Tasneem
T
Dyason
Jeffrey C
JC
Florio
Pas
P
Trower
Carolyn J
CJ
Thomson
Robin J
RJ
von Itzstein
Mark
M
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