Synthesis and evaluation of 4-O-alkylated 2-deoxy-2,3-didehydro-N-acetylneuraminic acid derivatives as inhibitors of human parainfluenza virus type-3 sialidase activity.

Abstract

The X-ray crystal structure of the paramyxoviral surface glycoprotein haemagglutinin-neuraminidase (HN) from Newcastle Disease virus was used as a template to design inhibitors of the HN from human parainfluenza virus type-3 (hPIV-3). 4-O-Alkylated derivatives of 2-deoxy-2,3-didehydro-N-acetylneuraminic acid (Neu5Ac2en), accessed from 8,9-O-isopropylidenated-Neu5Ac2en1Me, were found to inhibit the sialidase (neuraminidase) activity of hPIV-3 (strain C243) in the range of 3-30muM. This is comparable or improved activity compared to the parent 4-hydroxy compound.

• Authors: David J Tindal, Jeffrey C Dyason, Robin J Thomson, Takashi Suzuki, Hiroo Ueyama, Yohta Kuwahara, Naoyoshi Maki, Yasuo Suzuki, Mark von Itzstein
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 17 Issue 6 Pg. 1655-8 (Mar 15 2007) ISSN: 0960-894X [Print] England
• PMID: 17236768 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Enzyme Inhibitors
• Indicators and Reagents
• Neuraminidase
• N-Acetylneuraminic Acid

Topics

• Cell Line
• Crystallography, X-Ray
• Enzyme Inhibitors (chemical synthesis, pharmacology)
• Humans
• Indicators and Reagents
• N-Acetylneuraminic Acid (analogs & derivatives, chemical synthesis, pharmacology)
• Neuraminidase (antagonists & inhibitors)
• Parainfluenza Virus 3, Human (enzymology)
• Spectrometry, Fluorescence