Synthesis of Antiprotozoal 2--Imidazolines and Imidazoles and Their Evaluation on ILeishmania mexicana/I and ITrypanosoma cruzi/I

Twenty 2-(4-alkyloxyphenyl)-imidazolines and 2-(4-alkyloxyphenyl)-imidazoles were synthesized, with the former being synthesized in two steps by using MW and ultrasonication energy, resulting in good to excellent yields. Imidazoles were obtained in moderate yields by oxidizing imidazolines with MnO[sub.2] and MW energy. In response to the urgent need to treat neglected tropical diseases, a set of 2-(4-alkyloxyphenyl)- imidazolines and imidazoles was tested in vitro on Leishmania mexicana and Trypanosoma cruzi. The leishmanicidal activity of ten compounds was evaluated, showing an IC[sub.50] < 10 µg/mL. Among these compounds, 27–31 were the most active, with IC[sub.50] values < 1 µg/mL (similar to the reference drugs). In the evaluation on epimastigotes of T. cruzi, only 30 and 36 reached an IC[sub.50] < 1 µg/mL, showing better inhibition than both reference drugs. However, compounds 29, 33, and 35 also demonstrated attractive trypanocidal activities, with IC[sub.50] values < 10 µg/mL, similar to the values for benznidazole and nifurtimox.