Synergistic effect of zanamivir-porphyrin conjugates on inhibition of neuraminidase and inactivation of influenza virus

J Med Chem. 2009 Aug 13;52(15):4903-10. doi: 10.1021/jm900515g.

Abstract

New anti-influenza agents of tetravalent zanamivir on a porphyrin scaffold were synthesized. These compounds are 10 to 100 times more potent in inhibiting influenza replications even though they are somewhat less potent in neuraminidase inhibition than the monomeric zanamivir. The enhanced anti-influenza activity is probably attributable to the additional viral inactivation by singlet oxygen due to sensitization of the porphyrin moiety, which is brought in close proximity of virus by the conjugated zanamivir in a manner resembling the "magic bullet" mechanism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / chemical synthesis*
  • Antiviral Agents / pharmacology
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / pharmacology
  • Neuraminidase / antagonists & inhibitors*
  • Orthomyxoviridae / drug effects*
  • Orthomyxoviridae / physiology
  • Porphyrins / chemical synthesis*
  • Porphyrins / pharmacology
  • Virus Replication / drug effects
  • Zanamivir / analogs & derivatives*

Substances

  • Antiviral Agents
  • Enzyme Inhibitors
  • Porphyrins
  • Neuraminidase
  • Zanamivir