Alkyl and dialkylaminoethyl derivatives of 5-amino-2-azabicyclo[3.2.2]nonanes and their antiplasmodial and antitrypanosomal activities

Eur J Med Chem. 2010 Jan;45(1):179-85. doi: 10.1016/j.ejmech.2009.09.040. Epub 2009 Sep 30.

Abstract

N-Alkyl and N-(2-dialkylaminoethyl) derivatives of 5-amino-2-azabicyclo-nonanes were prepared and tested in vitro for their activities against the multidrug-resistant K1 strain of Plasmodium falciparum and Trypanosoma brucei rhodesiense (STIB 900). Most of the new compounds showed lower antitrypanosomal activity than their parent compounds. With respect to their activity against P. falciparum the N-alkyl derivatives exhibited worse selectivity due to decreased antiplasmodial activity or higher cytotoxicity. In comparison all of the new N-(2-dialkylaminoethyl) analogues possessed a much better selectivity and a single of these compounds showed even better antiplasmodial activity and selectivity than chloroquine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkanes / chemistry*
  • Alkanes / pharmacology*
  • Animals
  • Antiprotozoal Agents / chemistry*
  • Antiprotozoal Agents / pharmacology*
  • Cell Line
  • Hydrophobic and Hydrophilic Interactions
  • Inhibitory Concentration 50
  • Nitrogen / chemistry
  • Plasmodium falciparum / drug effects
  • Rats
  • Trypanosoma brucei rhodesiense / drug effects

Substances

  • Alkanes
  • Antiprotozoal Agents
  • Nitrogen
  • nonane