Synthesis and evaluation of the antitrypanosomal and antiplasmodial activities of new 4-aminobicyclo[2.2.2]octane derivatives

Eur J Med Chem. 2005 Sep;40(9):888-96. doi: 10.1016/j.ejmech.2005.03.018.

Abstract

Several new 4-amino-6,7-diphenylbicyclo[2.2.2]octane derivatives, methylthiosemicarbazones of bicyclo[2.2.2]octan-2-ones and esters of bicyclo[2.2.2]octan-2-ols were prepared. Their antitrypanosomal activities against Trypanosoma brucei rhodesiense (STIB 900) and their antiplasmodial activity against the K1 strain of Plasmodium falciparum (resistant to chloroquine and pyrimethamine) were investigated using microplate assays. In addition to that, the cytotoxicity of the new compounds was determined using L-6 cells. The methylthiosemicarbazones show moderate antiprotozoal activities whereas some of the esters of piperonylic acid, homopiperonylic acid and 2-naphtoic acid exhibit remarkable antitrypanosomal and antiplasmodial activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antimalarials / chemical synthesis*
  • Antimalarials / chemistry
  • Antimalarials / pharmacology*
  • Bridged Bicyclo Compounds / chemistry*
  • Cell Line
  • Inhibitory Concentration 50
  • Magnetic Resonance Spectroscopy
  • Molecular Structure
  • Myoblasts, Skeletal / drug effects
  • Parasitic Sensitivity Tests
  • Plasmodium falciparum / drug effects*
  • Rats
  • Trypanocidal Agents / chemical synthesis*
  • Trypanocidal Agents / chemistry
  • Trypanocidal Agents / pharmacology*
  • Trypanosoma brucei rhodesiense / drug effects*

Substances

  • 4-aminobicyclo(2.2.2)octane
  • Antimalarials
  • Bridged Bicyclo Compounds
  • Trypanocidal Agents