Bicyclo[2.2.2]octyl esters of dialkylamino acids as antiprotozoals

A couple of bicyclo[2.2.2]octyl esters of 2-dialkylaminoacetic acids were prepared. Their antiplasmodial and antitrypanosomal activities against Trypanosoma brucei rhodesiense (STIB 900) and the K1 strain of Plasmodium falciparum (resistant to chloroquine and pyrimethamine) were determined using microplate assays. Structure–activity relationships were discussed. The antiprotozoal activities were remarkably increased by insertion of a second basic centre. The selectivity indices of the most active compounds are superior in the bicyclo-octane series.

The newly prepared bicyclo[2.2.2]octyl esters are the so far most potent antimalarial and antitrypanosomal compounds of the bicyclo-octane series. The influence of the inserted dialkylamino groups on the antiprotozoal activity is remarkable. Furthermore, their selectivity indices have distinctly improved.Figure optionsDownload as PowerPoint slide