Trypanocidal activity of dicationic compounds related to pentamidine

Eight dicationic compounds related to pentamidine were studied for trypanoc idal activity in seven trypanosome isolates. In vitro studies revealed that diamidines are more potent than diimidazolines. For example, 2 (a diamidin e) and 4 (a diimidazoline) inhibited the growth of KETRI 243 with IC50 valu es of 2.3 and 900 nM, respectively. Introduction of polar groups into the l inker decreased the effectiveness of the compounds against drug-resistant t rypanosomes. In compounds with a 2-butene linker between the cationic group s, trans-isomers were more potent than cis-isomers. The cis- and trans-bute neamidines cured infection caused by Trypanosoma brucei brucei (EATRO Lab 1 10) and protected mice against infection by Trypanosoma brucei rhodesiense isolates, some of which are resistant to diamidines and melarsoprol. (C) 20 01 Editions scientifiques et medicales Elsevier SAS.