Microwave-assisted synthesis of C-8 aryl and heteroaryl inosines and determination of their inhibitory activities against Plasmodium falciparum purine nucleoside phosphorylase

Eur J Med Chem. 2014 Jul 23:82:459-65. doi: 10.1016/j.ejmech.2014.05.073. Epub 2014 Jun 2.

Abstract

8-Arylinosines have been scarcely studied for therapeutic purposes, probably due to difficulties in their synthesis. The recently described direct arylation reaction at position 8 of purine nucleosides has been employed to synthesize a series of 8-aryl and 8-pyridylinosines. These compounds have been studied for hydrolytic stability and subjected to biological evaluation. Three compounds have shown a pronounced specific inhibition of Plasmodium falciparum-encoded purine nucleoside phosphorylase, an important target for antimalarial chemotherapy.

Keywords: Antiviral; Direct C-arylation; Inosine; Microwave-assisted synthesis; Phosphorylase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Bacterial Agents / chemical synthesis
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Antiviral Agents / chemical synthesis
  • Antiviral Agents / chemistry
  • Antiviral Agents / pharmacology*
  • Cell Line, Tumor
  • Chlorocebus aethiops
  • DNA Viruses / drug effects
  • Dogs
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Escherichia coli / drug effects
  • HeLa Cells
  • Humans
  • Inosine / analogs & derivatives
  • Inosine / chemical synthesis
  • Inosine / pharmacology*
  • Madin Darby Canine Kidney Cells
  • Microbial Sensitivity Tests
  • Microwaves
  • Molecular Conformation
  • Mycoplasma hyorhinis / drug effects
  • Plasmodium falciparum / enzymology*
  • Purine-Nucleoside Phosphorylase / antagonists & inhibitors*
  • Purine-Nucleoside Phosphorylase / metabolism
  • RNA Viruses / drug effects
  • Vero Cells

Substances

  • Anti-Bacterial Agents
  • Antiviral Agents
  • Enzyme Inhibitors
  • Inosine
  • Purine-Nucleoside Phosphorylase