, , and Activities of Diamidines against Trypanosoma congolense and Trypanosoma vivax.

African animal trypanosomosis (AAT) is caused by the tsetse fly-transmitted protozoans and and leads to huge agricultural losses throughout sub-Saharan Africa. Three drugs are available to treat nagana in cattle (diminazene diaceturate, homidium chloride, and isometamidium chloride). With increasing reports of drug-resistant populations, new molecules should be investigated as potential candidates to combat nagana. Dicationic compounds have been demonstrated to have excellent efficacy against different kinetoplastid parasites. This study therefore evaluated the activities of 37 diamidines, using and drug sensitivity assays. The 50% inhibitory concentrations obtained ranged from 0.007 to 0.562 μg/ml for and from 0.019 to 0.607 μg/ml for On the basis of these promising results, 33 of these diamidines were further examined using mouse models of infection. Minimal curative doses of 1.25 mg/kg of body weight for both - and -infected mice were seen when the diamidines were administered intraperitoneally (i.p.) over 4 consecutive days. From these observations, 15 of these 33 diamidines were then further tested , using a single bolus dose for administration. The total cure of mice infected with and was seen with single i.p. doses of 5 and 2.5 mg/kg, respectively. This study identified a selection of diamidines which could be considered lead compounds for the treatment of nagana.