Antiplasmodial and antitrypanosomal activities of aminobicyclo[2.2.2]octyl omega-aminoalkanoates.
Several 4-aminobicyclo[2.2.2]octyl esters of omega-dialkylamino acids were prepared. Their activities against the multidrug-resistant K(1) strain of Plasmodium falciparum and Trypanosoma brucei rhodesiense (STIB 900) were determined using microplate assays and compared to those of formerly prepared analogues. The biological activity was influenced by the relative configuration in ring position 2, by the chain length of the acid moiety and by the amino substitution. The most active antiplasmodial ester was as active as chloroquine. One of the new compounds exhibited the highest antitrypanosomal activity and selectivity of all bicyclo-octane derivatives prepared so far.
Institute of Pharmaceutical Sciences, Pharmaceutical Chemistry, Karl-Franzens-University, Universitätsplatz 1, A-8010 Graz, Austria.
Christian
C
Schlapper
Werner
W
Seebacher
Johanna
J
Faist
Marcel
M
Kaiser
Reto
R
Brun
Robert
R
Saf
Robert
R
Weis
D000818:Animals; D000981:Antiprotozoal Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001643:Bridged Bicyclo Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D021261:Parasitic Sensitivity Tests; D010963:Plasmodium falciparum / Q000187:drug effects; D013329:Structure-Activity Relationship; D014344:Trypanocidal Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D016833:Trypanosoma brucei rhodesiense / Q000187:drug effects
D000981:Antiprotozoal Agents; D001643:Bridged Bicyclo Compounds; D014344:Trypanocidal Agents