Antimalarial activity of N(6)-substituted adenosine derivatives. Part 3

Bioorg Med Chem. 2004 Feb 15;12(4):755-62. doi: 10.1016/j.bmc.2003.11.008.

Abstract

A series of novel 3'-amido-3'-deoxy-N(6)-(1-naphthylmethyl)adenosines was synthesized applying a polymer-assisted solution phase (PASP) protocol and was tested for anti-malarial activity versus the Dd2 strain of Plasmodium falciparum. Further, this series and 62 adenosine derivatives were analyzed regarding 1-deoxy-d-xylulose 5-phosphate (DOXP) reductoisomerase inhibition. Biological evaluations revealed that the investigated 3',N(6)-disubstituted adenosine derivatives displayed moderate but significant activity against the P. falciparum parasite in the low-micromolar range. On the molecular level, DOXP reductoisomerase utilizing an adenosyl-containing substrate was identified as a promising metabolic target for ligands of adenosine binding motifs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine / chemical synthesis
  • Adenosine / chemistry*
  • Adenosine / pharmacology*
  • Aldose-Ketose Isomerases / antagonists & inhibitors
  • Aldose-Ketose Isomerases / metabolism
  • Animals
  • Antimalarials / chemical synthesis
  • Antimalarials / chemistry*
  • Antimalarials / pharmacology*
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology
  • Inhibitory Concentration 50
  • Molecular Structure
  • Multienzyme Complexes / antagonists & inhibitors
  • Multienzyme Complexes / metabolism
  • Oxidoreductases / antagonists & inhibitors
  • Oxidoreductases / metabolism
  • Plasmodium falciparum / drug effects
  • Plasmodium falciparum / enzymology

Substances

  • Antimalarials
  • Enzyme Inhibitors
  • Multienzyme Complexes
  • Oxidoreductases
  • 1-deoxy-D-xylulose 5-phosphate reductoisomerase
  • Aldose-Ketose Isomerases
  • Adenosine