Synthesis of C-4-modified zanamivir analogs as neuraminidase inhibitors and their anti-AIV activities. Academic Article uri icon

Overview

abstract

  • With the introduction of bioisosteres of the guanidinium group together with scaffold hopping, 35 zanamivir analogs with C-4-modification were synthesized, and their inhibitory activities against both group-1 and group-2 neuraminidase (H5N1 and H3N2) were determined. Compound D26 exerts the most potency, with IC(50) values of 0.58 and 2.72 μM against N2 and N1, respectively. Further preliminary anti-avian influenza virus (AIV, H5N1) activities against infected MDCK cells were evaluated, and D5 exerts ∼58% protective against AIV infection, which was comparable to zanamivir (∼67%). In a rat pharmacokinetic study, compound D5 showed an increased plasma half-life (t(1/2)) compared to zanamivir following either intravenous or oral administration. This study may represent a new start point for the future development of improved anti-AIV agents.

publication date

  • June 29, 2012

Research

keywords

  • Influenza A Virus, H3N2 Subtype
  • Influenza A Virus, H5N1 Subtype
  • Neuraminidase
  • Zanamivir

Identity

Scopus Document Identifier

  • 84864402401

Digital Object Identifier (DOI)

  • 10.1016/j.ejmech.2012.06.033

PubMed ID

  • 22795831

Additional Document Info

volume

  • 54