In Vitro and In Vivo Trypanosomicidal Action of Novel Arylimidamides against Trypanosoma cruzi

摘要: Arylimidamides (AIAs) have been shown to considerable biological activity against intracellular pathogens, includingTrypanosoma cruzi, which causes Chagas disease. In the present study, activities of 12 novel bis-AIAs and 2 mono-AIAs different strains ofT. cruziin vitroandin vivowere analyzed. The most active wasm-terphenyl bis-AIA (35DAP073), had a 50% effective concentration (EC50) 0.5 μM for trypomastigotes (Y strain), made it 26-fold more than benznidazole (Bz; 13 μM). It was also Colombiana strain (EC50= 3.8 Analysis forms Tulahuen showed that this 0.04 μM) about 100-fold Bz (2 trypanocidal effect dissociated from ability trigger lipid bodies within host cells, detected by oil red labeling. Both an compound (35DAP073) inactive (26SMB060) displayed similar activation profiles. Due their high selectivity indexes, two AIAs (35DAP073 35DAP081) were moved toin vivostudies, but because results acute toxicity assays, 35DAP081 excluded subsequent tests. findings obtained with 35DAP073 treatment infections caused Y revealed days therapy induced dose-dependent action, leading 96 46% reductions in level parasitemia. However, administration 10 daily doses animals infected resulted toxicity, preventing longer periods treatment. combination mg/kg body weight/day 100 mg/kg/day consecutive then assayed. Treatment suppression parasitemia, elimination neurological toxic effects, survival 100% animals. Quantitative PCR reduction parasite load (60%) compared achieved or amidine alone. Our support further investigations class aim developing alternatives