Design, synthesis, and in vitro antiprotozoal, antimycobacterial activities of N-{2-[(7-chloroquinolin-4-yl)amino]ethyl}ureas.
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.
Nava-Zuazo
Carlos
C
Facultad de Farmacia, Universidad Autónoma del Estado de Morelos, Cuernavaca, Morelos 62209, Mexico.
Estrada-Soto
Samuel
S
Guerrero-Alvarez
Jorge
J
León-Rivera
Ismael
I
Molina-Salinas
Gloria María
GM
Said-Fernández
Salvador
S
Chan-Bacab
Manuel Jesús
MJ
Cedillo-Rivera
Roberto
R
Moo-Puc
Rosa
R
Mirón-López
Gumersindo
G
Navarrete-Vazquez
Gabriel
G
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D000981:Antiprotozoal Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D015195:Drug Design; D016829:Giardia lamblia / Q000187:drug effects; D006801:Humans; D007894:Leishmania mexicana / Q000187:drug effects; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D011804:Quinolines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014508:Urea / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; D000981:Antiprotozoal Agents; D011804:Quinolines; D014508:Urea