Design, synthesis, and in vitro antiprotozoal, antimycobacterial activities of N-{2-[(7-chloroquinolin-4-yl)amino]ethyl}ureas.

Bioorganic & medicinal chemistry 2010 Jul 29; In press

Nava-Zuazo C, Estrada-Soto S, Guerrero-Álvarez J, León-Rivera I, Molina-Salinas G GM, Said-Fernández S, Chan-Bacab M MJ, Cedillo-Rivera R, Moo-Puc R, Mirón-López G, Navarrete-Vazquez G

Facultad de Farmacia, Universidad Autónoma del Estado de Morelos, Cuernavaca, Morelos 62209, Mexico.

We have synthesized a new series of quinoline tripartite hybrids from chloroquine, ethambutol, and isoxyl drugs, using a short synthetic route. Compounds 1-8 were tested in vitro against five protozoa (Giardia intestinalis, Trichomonas vaginalis,Entamoeba histolytica, Leishmania mexicana and Trypanosoma cruzi) and Mycobacterium tuberculosis. N-(4-Butoxyphenyl)-N'-{2-[(7-chloroquinolin-4-yl)amino]ethyl}urea (6) was the most active compound against all parasites tested. Compound 6 was 670 times more active than metronidazole, against G. intestinalis. It was as active as pentamidine against L. mexicana, and it was twofold more potent than ethambutol and isoxyl versus M. tuberculosis. This compound could be considered as a new broad spectrum antimicrobial agent.

Keywords: antimycobacterial antiprotozoal tuberculosis antimicrobial