Anti-flavivirus Activity of Different Tritylated Pyrimidine and Purine Nucleoside Analogues

  • ChemistryOpen. 2016 Jan 21;5(3):227-35. doi: 10.1002/open.201500216.
Christopher McGuigan  1 ,  Michaela Serpi  1 ,  Magdalena Slusarczyk  1 ,  Valentina Ferrari  1 ,  Fabrizio Pertusati  1 ,  Silvia Meneghesso  1 ,  Marco Derudas  1 ,  Laura Farleigh  2 ,  Paola Zanetta  2 ,  Joachim Bugert  2
Affiliations
  • 1. School of Pharmacy and Pharmaceutical Sciences Cardiff University King Edward VII Avenue Cardiff CF10 3NB United Kingdom.
  • 2. Medical Microbiology and Infectious Diseases School of Medicine Cardiff University Heath Park Cardiff CF14 4XN United Kingdom.
PMID: 27551659 DOI: 10.1002/open.201500216
Abstract

A series of tritylated and dimethoxytritylated analogues of selected pyrimidine and purine nucleosides were synthesized and evaluated for their in vitro inhibitory activity against two important members of the genus Flavivirus in the Flaviviridae family, the yellow fever (YFV) and dengue viruses (DENV). Among all compounds tested, the 5'-O-tritylated and the 5'-O-dimethoxytritylated 5-fluorouridine derivatives exerted potency against YFV. Interestingly in the series of purine analogues, the 5'O, N-bis-tritylated fludarabine derivative revealed strong inhibitory activity against DENV at μm concentrations, however significantly weaker potency against YFV.

Keywords
4,4′-dimetoxytrityl; antiviral; dengue; flavivirus; nucleoside analogues; trityl; yellow fever.
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