Synthesis and pharmacological evaluation of fluorescent and photoactivatable analogues of antiplasmodial naphthylisoquinolines

J Med Chem. 2007 Nov 29;50(24):6104-15. doi: 10.1021/jm061464w. Epub 2007 Nov 9.


The naphthylisoquinoline (NIQ) alkaloids from tropical Ancistrocladaceae and Dioncophyllaceae plants show high antiplasmodial activities in vitro and in vivo, even against chloroquine-resistant strains of the malaria pathogen. For the directed optimization of these activities, an investigation of the mode of action seems most rewarding. We have therefore embarked on the identification of the respective target protein in Plasmodium falciparum. For this purpose, we have developed a flexible pathway for the synthesis of a chemically divergent series of photoactive and fluorescent derivatives of such alkaloids and succeeded in preparing the first functionalized NIQ derivatives, 10, 12, and 35, suited for fluorescence and photoaffinity labeling experiments. Pharmacological investigations ensured that the modified alkaloid derivatives retained their antiplasmodial activity. The work may pave the way for a further improvement of the activity of these natural products and will thus increase their pharmacological potential as a valuable lead structure against the widespread tropical disease malaria.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaloids / chemical synthesis*
  • Alkaloids / chemistry
  • Alkaloids / pharmacology
  • Animals
  • Antimalarials / chemical synthesis*
  • Antimalarials / chemistry
  • Antimalarials / pharmacology
  • Fluorescent Dyes / chemical synthesis*
  • Fluorescent Dyes / chemistry
  • Fluorescent Dyes / pharmacology
  • Isoquinolines / chemical synthesis*
  • Isoquinolines / chemistry
  • Isoquinolines / pharmacology
  • Naphthalenes / chemical synthesis*
  • Naphthalenes / chemistry
  • Naphthalenes / pharmacology
  • Photoaffinity Labels / chemical synthesis*
  • Photoaffinity Labels / chemistry
  • Photoaffinity Labels / pharmacology
  • Plasmodium falciparum / drug effects*
  • Plasmodium falciparum / metabolism
  • Structure-Activity Relationship


  • Alkaloids
  • Antimalarials
  • Fluorescent Dyes
  • Isoquinolines
  • Naphthalenes
  • Photoaffinity Labels
  • dioncophylline A