Five bis-arylimidamides were assayed as anti- agents by , , and approaches. None were considered to be pan-assay interference compounds. They had a favorable pharmacokinetic landscape and were active against trypomastigotes and intracellular forms, and in combination with benznidazole, they gave no interaction. The most selective agent (28SMB032) tested led to a 40% reduction in parasitemia (0.1 mg/kg of body weight/5 days intraperitoneally) but without mortality protection. target fishing suggested DNA as the main target, but ultrastructural data did not match.