Synthesis and antiprotozoal activity of some 2-(trifluoromethyl)-1H-benzimidazole bioisosteres.
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.
Navarrete-Vázquez
Gabriel
G
Facultad de Farmacia, Universidad Autónoma del Estado de Morelos, Cuernavaca Morelos 62210, México. gabriel_navarrete@uaem.mx
Rojano-Vilchis
María de Monserrat
Mde M
Yépez-Mulia
Lilián
L
Meléndez
Víctor
V
Gerena
Lucia
L
Hernández-Campos
Alicia
A
Castillo
Rafael
R
Hernández-Luis
Francisco
F
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*
D000962:Antimalarials; D000981:Antiprotozoal Agents; D001562:Benzimidazoles; D008795:Metronidazole; C031000:benzimidazole; D015766:Albendazole