Currently, 7 to 8 million people are affected by Chagas disease, a parasitosis caused by T. cruzi. Treatment of this disease is inadequate because there are only two drugs available and both can cause serious adverse effects and aren't active in the chronic phase of the disease. Semicarbazones and thiosemicarbazones derivatives showed inhibition against cruzain, the major cysteine protease in T. cruzi. In this work, analogues of nitrofurazone antichagasic candidates were designed by bioisosterism. In molecular modeling and docking studies the thiosemicarbazone derivatives showed a good complementarity with the active site of cruzain. Six semicarbazone, thiosemicarbazone and aminoguanidine derivatives were synthesized and tested in cruzain inhibitory assays and against T. cruzi epimastigote forms. Compounds presented significant cruzain inhibition between 70 and 75%. The IC50 values observed in epimastigotes forms of T. cruzi ranged from 19.8 to 139.45 �M. The compounds did not presented cytotoxicity at concentrations up to 50 �M and 250 �M in MTT tests. This study shows that this class of compounds can be used as a prototype in the search for new antichagasic drugs.

Nitrofurazone bioisosters (semicarbazone, thiosemicarbazone and aminoguanidine derivatives) as antichagasic candidates

248th National Meeting (2014)

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