Antiplasmodial and antitrypanosomal activities of aminobicyclo[2.2.2]octyl ω-aminoalkanoates

Several 4-aminobicyclo[2.2.2]octyl esters of ω-dialkylamino acids were prepared. Their activities against the multidrug-resistant K1 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.

Graphical abstract Synthesis of bicyclic compounds with improved antiprotozoal activity.Figure optionsDownload full-size imageDownload as PowerPoint slide