Design, synthesis, and biological evaluation of crenatoside analogues as novel influenza neuraminidase inhibitors

Eur J Med Chem. 2016 Feb 15:109:199-205. doi: 10.1016/j.ejmech.2015.12.031. Epub 2016 Jan 4.

Abstract

Natural products, especially derived from TCMH, have been found to exert antiviral effects against influenza virus. Crenatoside, a phenylethanoid glycoside from Pogostemon cablin Benth, which has been shown as a novel effective NA inhibitor previously, is considered as the leading compound for our further SARs studies. This work presented design, synthesis of novel crenatoside analogues from readily available d-Glucose and l-rhamnose in a convergent manner. Furthermore, their biological activities and SARs were also investigated. Especially, compound 2 h showed impressive IC50 = 27.77 μg/mL against NAs, which is 3 folds more potent than the leading compound crenatoside (IC50 = 89.81 μg/mL). These results would promise their therapeutic potential for influenza disease.

Keywords: Crenatoside derivatives; Design; Influenza virus; Neuraminidases inhibitors; Synthesis.

MeSH terms

  • Antiviral Agents / chemistry*
  • Antiviral Agents / pharmacology*
  • Caffeic Acids / chemistry*
  • Caffeic Acids / pharmacology*
  • Drug Design
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology
  • Glucosides / chemistry*
  • Glucosides / pharmacology*
  • Humans
  • Influenza A Virus, H1N1 Subtype / drug effects
  • Influenza A Virus, H1N1 Subtype / enzymology
  • Influenza A virus / drug effects
  • Influenza A virus / enzymology*
  • Influenza, Human / drug therapy
  • Influenza, Human / virology
  • Models, Molecular
  • Neuraminidase / antagonists & inhibitors*
  • Neuraminidase / metabolism
  • Structure-Activity Relationship

Substances

  • Antiviral Agents
  • Caffeic Acids
  • Enzyme Inhibitors
  • Glucosides
  • crenatoside
  • Neuraminidase