Antiprotozoal activities of new bicyclo[2.2.2]octan-2-imines and esters of bicyclo[2.2.2]octan-2-ols.
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).
Seebacher
Werner
W
Institute of Pharmaceutical Sciences, Pharmaceutical Chemistry, Karl-Franzens University, Universitätsplatz 1, A-8010 Graz, Austria. we.seebacher@uni-graz.at
Schlapper
Christian
C
Brun
Reto
R
Kaiser
Marcel
M
Saf
Robert
R
Weis
Robert
R
D000818:Animals; D000981:Antiprotozoal Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D001643:Bridged Bicyclo Compounds / Q000138:chemical synthesis / Q000494:pharmacology*; D004952:Esters; D007097:Imines / Q000138:chemical synthesis / Q000494:pharmacology*; D000442:Octanols / Q000138:chemical synthesis / Q000494:pharmacology*; D010963:Plasmodium falciparum / Q000187:drug effects / Q000502:physiology; D016833:Trypanosoma brucei rhodesiense / Q000187:drug effects / Q000502:physiology
D000981:Antiprotozoal Agents; D001643:Bridged Bicyclo Compounds; D004952:Esters; D007097:Imines; D000442:Octanols