RESUMO
The present work reports the synthesis and biological activity of a series of 14 benzimidazole derivatives designed to act on the enzyme triosephosphate isomerase of Trypanosoma cruzi (TcTIM). This enzyme is involved in the metabolism of glucose, the only source of energy for the parasite. In this study, we found four compounds that inhibit TcTIM moderately and lack inhibitory activity against human TIM (HsTIM). In vitro studies against T. cruzi epimastigotes showed two compounds that were more active than the reference drug nifurtimox, and these presented a low cytotoxic effect in mouse macrophages (J744 cell line).
Assuntos
Benzimidazóis/síntese química , Benzimidazóis/farmacologia , Trypanosoma cruzi/efeitos dos fármacos , Animais , Antiparasitários/síntese química , Antiparasitários/química , Antiparasitários/farmacologia , Benzimidazóis/química , Humanos , Concentração Inibidora 50 , Camundongos , Estrutura MolecularRESUMO
A series of twelve new 2-(methylthio)-1H-benzimidazole-5-carboxamide derivatives (1-12) were synthesized and their antiparasitic activity was tested in vitro against Giardia intestinalis, Trichomonas vaginalis and Entamoeba histolytica. Experimental evaluations showed IC50 values within the nanomolar range for all tested compounds, some showing higher activity than metronidazole and albendazole. A chemoinformatic study was used to compare the structure-activity relationship of the synthesized carboxamides with those of 91 previously studied benzimidazoles, and with some Nitazoxanide-N-methylbenzimidazole hybrids recently synthetized by our group. Compounds 1 and 3 were identified as prominent selective compounds against T. vaginalis and G. intestinalis, respectively, while compound 4 was found to be of broad spectrum against the three protozoans.