Synthesis and biological activities of novel artemisinin derivatives as cysteine protease falcipain-2 inhibitors

Arch Pharm Res. 2012 Sep;35(9):1525-31. doi: 10.1007/s12272-012-0902-4. Epub 2012 Oct 9.

Abstract

A series of novel artemisinin derivatives were synthesized from artemisinin and different anilines. All compounds were obtained as β-isomers. The target compounds were evaluated for inhibition activity against Plasmodium falciparum falcipain-2 in vitro, and most of them exhibited potent inhibition in the low micromolar range and proved to be new types of falcipain-2 inhibitors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aniline Compounds / chemistry
  • Antimalarials / chemistry*
  • Antimalarials / metabolism
  • Antimalarials / pharmacology*
  • Artemisinins / chemistry*
  • Artemisinins / metabolism
  • Artemisinins / pharmacology*
  • Catalytic Domain / drug effects
  • Cysteine Endopeptidases / chemistry
  • Cysteine Endopeptidases / genetics
  • Cysteine Endopeptidases / metabolism
  • Cysteine Proteinase Inhibitors / chemistry*
  • Cysteine Proteinase Inhibitors / metabolism
  • Cysteine Proteinase Inhibitors / pharmacology*
  • Drug Design
  • Magnetic Resonance Spectroscopy
  • Molecular Docking Simulation
  • Osmolar Concentration
  • Plasmodium falciparum / enzymology
  • Protein Binding
  • Protein Structure, Secondary / drug effects
  • Protozoan Proteins / antagonists & inhibitors*
  • Protozoan Proteins / chemistry
  • Protozoan Proteins / genetics
  • Protozoan Proteins / metabolism
  • Recombinant Proteins / antagonists & inhibitors
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / metabolism
  • Stereoisomerism
  • Structure-Activity Relationship
  • Thiosemicarbazones / chemistry
  • Thiosemicarbazones / metabolism
  • Thiosemicarbazones / pharmacology
  • Transition Temperature

Substances

  • Aniline Compounds
  • Antimalarials
  • Artemisinins
  • Cysteine Proteinase Inhibitors
  • Protozoan Proteins
  • Recombinant Proteins
  • Thiosemicarbazones
  • artemisinin
  • Cysteine Endopeptidases
  • falcipain 2