Antiprotozoal activities of new bicyclo[2.2.2]octan-2-imines and esters of bicyclo[2.2.2]octan-2-ols

Eur J Pharm Sci. 2005 Mar;24(4):281-9. doi: 10.1016/j.ejps.2004.11.003. Epub 2004 Dec 29.

Abstract

Several bicyclo[2.2.2]octan-2-imines and esters of bicyclo[2.2.2]octan-2-ols were prepared. Their antitrypanosomal and antiplasmodial activities against Trypanosoma brucei rhodesiense (STIB 900) and the K1 strain of Plasmodium falciparum (resistant to chloroquine and pyrimethamine) were determined using microplate assays. Two of the synthesized bicyclo[2.2.2]octan-2-one 4'-phenylthiosemicarbazones showed the highest antitrypanosomal activity (IC(50)<0.3 microM) of the so far prepared 4-amino-6,7-diarylbicyclo[2.2.2]octane derivatives, but they are distinctly less active than suramine (IC(50)=0.0075 microM). Most of the 4'-phenylthiosemicarbazones and a single bicyclo[2.2.2]octan-2-yl benzoate exhibit attractive antimalarial activity (IC(50)=0.23-0.72 microM). Two bicyclooctanone oximes are even as active as chloroquine (IC(50)=0.08-0.15 microM, chloroquine: IC(50)=0.12 microM against sensitive strains).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antiprotozoal Agents / chemical synthesis
  • Antiprotozoal Agents / pharmacology*
  • Bridged Bicyclo Compounds / chemical synthesis
  • Bridged Bicyclo Compounds / pharmacology*
  • Esters
  • Imines / chemical synthesis
  • Imines / pharmacology*
  • Octanols / chemical synthesis
  • Octanols / pharmacology*
  • Plasmodium falciparum / drug effects
  • Plasmodium falciparum / physiology
  • Trypanosoma brucei rhodesiense / drug effects
  • Trypanosoma brucei rhodesiense / physiology

Substances

  • Antiprotozoal Agents
  • Bridged Bicyclo Compounds
  • Esters
  • Imines
  • Octanols