title: Synthesis and antiprotozoal activity of some 2-(trifluoromethyl)-1H-benzimidazole bioisosteres.
abstract: A series of 2-(trifluoromethyl)-1H-benzimidazole derivatives with various 5- and 6-position bioisosteric substituents (-Cl, -F, -CF3, -CN), namely 1-7, were prepared using a short synthetic route. Each analogue was tested in vitro against the protozoa Giardia intestinalis and Trichomonas vaginalis in comparison with albendazole and metronidazole. Several analogues had IC50 values < 1 microM against both species, which make them significantly more potent than either standard. Compound 4 [2,5(6)-bis(trifluoromethyl)-1H-benzimidazole], was 14 times more active than albendazole against T. vaginalis. This compound (4) also showed moderate antimalarial activity against W2 and D6 strains of Plasmodium falciparum (5.98 and 6.12 microM, respectively). Studying further structure activity relationships through the use of bioisosteric substitution in these benzimidazolic derivatives should provide new leads against protozoal and possibly malarial diseases.
authors.affiliation: Facultad de Farmacia, Universidad Autónoma del Estado de Morelos, Cuernavaca Morelos 62210, México. gabriel_navarrete@uaem.mx
authors.forename: Gabriel
authors.initials: G
authors.lastname: Navarrete-Vázquez
authors.forename: María de Monserrat
authors.initials: Mde M
authors.lastname: Rojano-Vilchis
authors.forename: Lilián
authors.initials: L
authors.lastname: Yépez-Mulia
authors.forename: Víctor
authors.initials: V
authors.lastname: Meléndez
authors.forename: Lucia
authors.initials: L
authors.lastname: Gerena
authors.forename: Alicia
authors.initials: A
authors.lastname: Hernández-Campos
authors.forename: Rafael
authors.initials: R
authors.lastname: Castillo
authors.forename: Francisco
authors.initials: F
authors.lastname: Hernández-Luis
mesh_terms: D015766:Albendazole / Q000138:chemical synthesis / Q000494:pharmacology; D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis / Q000494:pharmacology; D000981:Antiprotozoal Agents / Q000138:chemical synthesis / Q000494:pharmacology; D001562:Benzimidazoles / Q000138:chemical synthesis / Q000494:pharmacology; D016829:Giardia lamblia / Q000187:drug effects*; D005873:Giardiasis / Q000188:drug therapy; D020128:Inhibitory Concentration 50; D016778:Malaria, Falciparum / Q000188:drug therapy; D008795:Metronidazole / Q000138:chemical synthesis / Q000494:pharmacology; D015394:Molecular Structure; D021261:Parasitic Sensitivity Tests; D010963:Plasmodium falciparum / Q000187:drug effects; D013329:Structure-Activity Relationship; D014245:Trichomonas Infections / Q000188:drug therapy; D014246:Trichomonas vaginalis / Q000187:drug effects*
chemical_list: D000962:Antimalarials; D000981:Antiprotozoal Agents; D001562:Benzimidazoles; D008795:Metronidazole; C031000:benzimidazole; D015766:Albendazole