title: Synthesis and in vitro trichomonicidal, giardicidal and amebicidal activity of N-acetamide(sulfonamide)-2-methyl-4-nitro-1H-imidazoles.
abstract: Two new series of imidazole derivatives (acetamides: 1-8 and sulfonamides: 9-15) were synthesized using a short synthetic route. Compound 1 as well as the intermediate 16g were characterized by X-ray crystallography. Imidazole derivatives 1-15 were tested in vitro against three unicellular parasites (Giardia intestinalis, Trichomonas vaginalis and Entamoeba histolytica) in comparison with benznidazole (Bzn) and metronidazole. Compound 1 [N-benzyl-2-(2-methyl-4-nitro-1H-imidazol-1-yl)acetamide] was 2 times more active than Bzn against T. vaginalis and G. intestinalis and it was as active as Bzn against E. histolytica. Sulfonamides showed selective toxicity against E. histolytica over the other parasites. Toxicity assay showed that all compounds are non-cytotoxic against MDCK cell line. The results revealed that compounds 1-15 have antiparasitic bioactivity in the micromolar range against the parasites tested, and could be considered as benznidazole bioisosteres.
authors.affiliation: Facultad de Farmacia, Universidad Autónoma del Estado de Morelos, Cuernavaca, Morelos, Mexico.
authors.forename: Emanuel
authors.initials: E
authors.lastname: Hernández-Núñez
authors.forename: Hugo
authors.initials: H
authors.lastname: Tlahuext
authors.forename: Rosa
authors.initials: R
authors.lastname: Moo-Puc
authors.forename: Héctor
authors.initials: H
authors.lastname: Torres-Gómez
authors.forename: Reyna
authors.initials: R
authors.lastname: Reyes-Martínez
authors.forename: Roberto
authors.initials: R
authors.lastname: Cedillo-Rivera
authors.forename: Carlos
authors.initials: C
authors.lastname: Nava-Zuazo
authors.forename: Gabriel
authors.initials: G
authors.lastname: Navarrete-Vazquez
mesh_terms: D000818:Animals; D000981:Antiprotozoal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D019295:Computational Biology; D018360:Crystallography, X-Ray; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D004748:Entamoeba histolytica / Q000187:drug effects*; D016829:Giardia lamblia / Q000187:drug effects*; D007093:Imidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D009593:Nitroimidazoles / Q000737:chemistry; D014246:Trichomonas vaginalis / Q000187:drug effects*
chemical_list: D000981:Antiprotozoal Agents; D007093:Imidazoles; D009593:Nitroimidazoles; C009999:benzonidazole