Synthesis of Antiprotozoal 2-(4-Alkyloxyphenyl)-Imidazolines and Imidazoles and Their Evaluation on <i>Leishmania mexicana</i> and <i>Trypanosoma cruzi</i>

Abstract

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 MnO2 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 IC50 27–31 were the most active, with IC50 values T. cruzi, only 30 and 36 reached an IC50 29, 33, and 35 also demonstrated attractive trypanocidal activities, with IC50 values < 10 µg/mL, similar to the values for benznidazole and nifurtimox.

Keywords

• imidazoline synthesis
• imidazole synthesis
• Chagas disease
• <i>Leishmania mexicana</i>
• <i>Trypanosoma cruzi</i>