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Neuraminidase Inhibitors (neuraminidase + inhibitor)

Distribution by Scientific Domains
Chemistry66%

Selected Abstracts

Synthesis and Biological Evaluation of Non-Hydrolyzable 1,2,3-Triazole-Linked Sialic Acid Derivatives as Neuraminidase Inhibitors

EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 16 2009
Michel Weïwer
Abstract ,-Sialic acid azide 1 has been used as a substrate for the efficient preparation of 1,2,3-triazole derivatives of sialic acid using the copper-catalyzed azide,alkyne Huisgen cycloaddition ("click chemistry"). Our approach is to generate non-natural N-glycosides of sialic acid that are resistant to neuraminidase-catalyzed hydrolysis as opposed to the natural O-glycosides. These N-glycosides would act as neuraminidase inhibitors to prevent the release of new virions. As a preliminary study, a small library of 1,2,3-triazole-linked sialic acid derivatives has been synthesized in 71,89,% yield. A disaccharide mimic of sialic acid has also been prepared using the ,-sialic acid azide 1 and a C-8 propargyl sialic acid acceptor in 68,% yield. A model sialic acid coated dendrimer was also synthesized from a perpropargylated pentaerythritol acceptor. These novel sialic acid derivatives were then evaluated as potential neuraminidase inhibitors using a 96-well plate fluorescence assay; micromolar IC50 values wereobserved, comparable to the known sialidase inhibitorNeu5Ac2en.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009) [source]

Influenza Virus Neuraminidase Inhibitors: Generation and Comparison of Structure-Based and Common Feature Pharmacophore Hypotheses and Their Application in Virtual Screening.

CHEMINFORM, Issue 51 2004
Theodora Steindl
No abstract is available for this article. [source]

Role of sialic acid in bovine sperm,zona pellucida binding

MOLECULAR REPRODUCTION & DEVELOPMENT, Issue 5 2007
José Guillermo Velásquez
Abstract Sperm binding activity has been detected in zona pellucida (ZP) glycoproteins and it is generally accepted that this activity resides in the carbohydrate moieties. In the present study we aim to identify some of the specific carbohydrate molecules involved in the bovine sperm,ZP interaction. We performed sperm binding competition assays, in vitro fecundation (IVF) in combination with different lectins, antibodies and neuraminidase digestion, and chemical and cytochemical analysis of the bovine ZP. Both MAA lectin recognising ,-2,3-linked sialic acid and neuraminidase from Salmonella typhimurium with catalytic activity for ,-2,3-linked sialic acid, demonstrated a high inhibitory effect on the sperm,ZP binding and oocyte penetration. These results suggest that bovine sperm,ZP binding is mediated by ,-2,3-linked sialic acid. Experiments with trisaccharides (sialyllactose, 3,-sialyllactosamine and 6,-sialyllactosamine) and glycoproteins (fetuin and asialofetuin) corroborated this and suggest that at least the sequence Neu5Ac(,2-3)Gal(,1-4)GlcNAc is involved in the sperm,ZP interaction. Moreover, these results indicate the presence of a sperm plasma membrane specific protein for the sialic acid. Chemical analysis revealed that bovine ZP glycoproteins contain mainly Neu5Ac (84.5%) and Neu5GC (15.5%). These two types of sialic acid residues are probably linked to Gal,1,4GlcNAc and GalNAc by ,-2,3- and ,-2,6-linkages, respectively, as demonstrated by lectin cytochemical analysis. The use of a neuraminidase inhibitor resulted in an increased number of spermatozoa bound to the ZP and penetrating the oocyte. From this last result we hypothesize that a neuraminidase from cortical granules would probably participate in the block to polyspermy by removing sialic acid from the ZP. Mol. Reprod. Dev. 74: 617,628, 2007. © 2006 Wiley-Liss, Inc. [source]

Synthesis and Biological Evaluation of Non-Hydrolyzable 1,2,3-Triazole-Linked Sialic Acid Derivatives as Neuraminidase Inhibitors

EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 16 2009
Michel Weïwer
Abstract ,-Sialic acid azide 1 has been used as a substrate for the efficient preparation of 1,2,3-triazole derivatives of sialic acid using the copper-catalyzed azide,alkyne Huisgen cycloaddition ("click chemistry"). Our approach is to generate non-natural N-glycosides of sialic acid that are resistant to neuraminidase-catalyzed hydrolysis as opposed to the natural O-glycosides. These N-glycosides would act as neuraminidase inhibitors to prevent the release of new virions. As a preliminary study, a small library of 1,2,3-triazole-linked sialic acid derivatives has been synthesized in 71,89,% yield. A disaccharide mimic of sialic acid has also been prepared using the ,-sialic acid azide 1 and a C-8 propargyl sialic acid acceptor in 68,% yield. A model sialic acid coated dendrimer was also synthesized from a perpropargylated pentaerythritol acceptor. These novel sialic acid derivatives were then evaluated as potential neuraminidase inhibitors using a 96-well plate fluorescence assay; micromolar IC50 values wereobserved, comparable to the known sialidase inhibitorNeu5Ac2en.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009) [source]

Treatment of epidemic and pandemic influenza with neuraminidase and M2 proton channel inhibitors

CLINICAL MICROBIOLOGY AND INFECTION, Issue 1 2003
J. S. Oxford
A small armentarium of anti-influenza drugs now exists, and includes the M2 blockers (amantadine and rimantadine) and the neuraminidase inhibitors (Relenza and Tamiflu). The neuraminidase inhibitors have certain advantages, including a broader spectrum of antiviral activity, including influenza A and B viruses. On the other hand, there is now much clinical experience with the M2 blockers, and these drugs are inexpensive. It is clear that influenza in different community groups needs to be managed in specific and targeted ways. For example, in the over-65-years and at-risk groups, vaccination will remain a mainstay of disease prevention. However, up to 40% of those in these groups may fail to receive vaccine, and therefore the antivirals can be used therapeutically, or, in defined circumstances, as prophylactics. At present, influenza is hardly managed in the community. The infrequent global outbreaks, pandemics, present further problems. The more extensive use of the two classes of antivirals, and also vaccines, in the important interpandemic years will provide a very significant investment in health benefits in the face of a new pandemic virus in an otherwise completely vulnerable population. [source]