Parasitic diseases are a public health problem affecting millions of people worldwide. One\nof the scaffolds used in several drugs for the treatment of parasitic diseases is the benzimidazole\nmoiety, a heterocyclic aromatic compound. This compound is a crucial pharmacophore group\nand is considered a privileged structure in medicinal chemistry. In this study, the benzimidazole\ncore served as a model for the synthesis of a series of 2-(2-amino-5(6)-nitro-1H-benzimidazol-1\n-yl)-N-arylacetamides 1ââ?¬â??8 as benznidazole analogues. The in silico pharmacological results calculated\nwith PASS platform exhibited chemical structures highly similar to known antiprotozoal drugs.\nCompounds 1ââ?¬â??8 when evaluated in silico for acute toxicity by oral dosing, were less toxic than\nbenznidazole. The synthesis of compounds 1ââ?¬â??8 were carried out through reaction of 5(6)-nitro-\n1H-benzimidazol-2-amine (12) with 2-chlroactemides 10aââ?¬â??h, in the presence of K2CO3 and acetonitrile\nas solvent, showing an inseparable mixture of two regioisomers with the -NO2 group in position 5\nor 6 with chemical yields of 60 to 94%. The prediction of the NMR spectra of molecule 1 coincided\nwith the experimental chemical displacements of the regioisomers. Comparisons between the NMR\nprediction and the experimental data revealed that the regioisomer endo-1,6-NO2 predominated in\nthe reaction. The in vitro antiparasitic activity of these compounds on intestinal unicellular parasites\n(Giardia intestinalis and Entamoeba histolytica) and a urogenital tract parasite (Trichomonas vaginalis)\nwere tested. Compound 7 showed an IC50 of 3.95 Ã?¼Mand was 7 time more active against G. intestinalis\nthan benznidazole. Compounds 7 and 8 showed 4 times more activity against T. vaginalis compared\nwith benznidazole.
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