Novel Anti-Influenza Drugs

  • Author: ChemViews
  • Published Date: 15 February 2011
  • Source / Publisher: Chemistry - An Asian Journal/Wiley-VCH
  • Copyright: Wiley-VCH Verlag GmbH & Co. KGaA
thumbnail image: Novel Anti-Influenza Drugs

Neuraminidases (NAs) regulate interactions with the extracellular world including infection, immunity, and cell–cell adhesion. Many pathogens utilize their own NAs, making NA inhibitors an attractive target for drug discovery.

A potent inhibitor for Vibrio cholerae neuraminidase (VCNA) – one of the oldest and best studied NA involved in cholera
pathogenesis – has been developed by Hiroshi Hinou and colleagues, Hokkaido University, Japan. Mechanism-based labeling study revealed the presence of a potential target loop for VCNA inhibition. The results were then used to prepare a focused library of 187 compounds. A [2+3] cyclization (click reaction) was used to prepare derivatives of DANA (2,3-dehydro-N-acetylneuraminic acid).

A N-trifluoroacetyl derivative of DANA, FANA, was identified as a potential inhibitor along with DANA analogue modified at the C9 position (see below). Validation studies suggested that the 9-substitution group interacted hydrophobically with the target loop moiety, adding a noncompetitive inhibition property to the DANA skeleton.

VCNA has an active site very similar to that observed in influenza (Flu) NA and Salmonella NA, meaning this two-step strategy presents a new route for the design of structurally novel anti-influenza drugs.

Image: (c) Wiley-VCH

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Magazine of Chemistry Europe (16 European Chemical Societies) published by Wiley-VCH