Pharmacophore Analysis of Trypanosoma cruzi Trypanothione Reductase (TR) Complexed with Peptide Mimetic Inhibitors [Análise Farmacofórica da Tripanotiona Redutase (TR) de Trypanosoma cruzi Complexada com Inibidores Peptídeo Miméticos]

The treatment of Chagas disease in its chronic form is inefficient and thus new therapeutic approaches have been studied. Among these, the Trypanothione Reductase (TR) is presented as a selective and specific target for chemotherapy of this disease. We studied, by molecular dynamics (MD) using the program GROMACS, the behavior of a series of six complexes involving Trypanosoma cruzi TR and its peptide mimetic inhibitors. This methodology allows the temporal evaluation of multiple conformations of the atoms together with their interactions in each complex. The results revealed some residues in the active site that modulates the enzyme inhibition profile (pharmacophoric groups). From this pharmacophoric analysis, it was possible to select alternative binding sites into the enzyme and we identified some interactions patterns that govern the inhibition of this class of compounds. These informations will be exploited in the rational development of inhibitors of TR aiming to treat Chagas disease.