Alkyl and dialkylaminoethyl derivatives of 5-amino-2-azabicyclo[3.2.2]nonanes and their antiplasmodial and antitrypanosomal activities.
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.
Faist
Johanna
J
Institute of Pharmaceutical Sciences, Pharmaceutical Chemistry, Karl-Franzens-University, Universitätsplatz 1, A-8010 Graz, Austria.
Seebacher
Werner
W
Kaiser
Marcel
M
Brun
Reto
R
Saf
Robert
R
Weis
Robert
R
D000473:Alkanes / Q000737:chemistry* / Q000494:pharmacology*; D000818:Animals; D000981:Antiprotozoal Agents / Q000737:chemistry* / Q000494:pharmacology*; D002460:Cell Line; D057927:Hydrophobic and Hydrophilic Interactions; D020128:Inhibitory Concentration 50; D009584:Nitrogen / Q000737:chemistry; D010963:Plasmodium falciparum / Q000187:drug effects; D051381:Rats; D016833:Trypanosoma brucei rhodesiense / Q000187:drug effects
D000473:Alkanes; D000981:Antiprotozoal Agents; D009584:Nitrogen; C017573:nonane