Novel iodotyramides with para-substituted benzoic acids were synthesized via electrophilic aromatic substitutions and amide coupling via N,N'-diisopropylcarbodiimide (DIC) in dimethylformamide (DMF). All derivatives were in vitro screened against U-937 macrophages and Plasmodium falciparum, Leishmania panamensis and Trypanosoma cruzi protozoan parasites. The hemolytic activity was evaluated on human red blood cells (RBC). Compounds N-(4-hydroxy-3,5-diiodophenethyl)-4-methylbenzamide and N-(3,5-diiodo-4-methoxyphenethyl)-4-methoxybenzamide were the most active against L. panamensis with an effective concentration 50 (EC50) of 17.9 and 17.5 µg mL-1, respectively; while compounds N-(3,5-diiodo-4-methoxyphenethyl)-4-methylbenzamide and N-(3,5-diiodo-4-methoxyphenethyl)-4-methoxybenzamide were the most active for T. cruzi with EC50 values of 23.75 and 6.19 µg mL-1, respectively. In contrast, all derivatives showed high activity against P. falciparum with EC50 < 25 µg mL-1, except compound N-(4-hydroxy-3,5-diiodophenethyl)-benzamide. No compound was hemolytic over RBC. This report represents the importance of novel iodotyramides as anti-parasites agents.
Keywords:
anti-protozoan activity; cytotoxicity; L. panamensis; P. falciparum; T. cruzi; iodotyramides
