The protozoan Trypanosoma cruzi (T. cruzi) depends on the glycolysis pathway as its sole source of energy. The enzyme triosaphosphate isomerase (TIM), is an important enzyme involved in this pathway, being a target for drug design. Therefore, in this study a virtual screening based on the benzimidazole substructure of the ZINC15 database was performed, the obtained compounds that met the Lipinski rule were brought to molecular docking at the T. cruzi TIM (TcTIM) interface, compounds with the most negative docking scores (PA) with respect to the previously established cut-off value of -8.9 kcal/mol were selected as potential TcTIM inhibitors. 1604 molecules with PA between -10.6 and -8.9 kcal/mol were obtained, these compounds were grouped by structure and interaction profile. The most representative compounds of each group according to their PA (selecting eight compounds) were analyzed by molecular dynamics simulation. This analysis allowed to determine the stability of the complex formed in the molecular docking by means of an RMSD graph where the compound B2 presented a fluctuation from 1.94 to 6.5 Å, being this the most stable compound in time (100 ns), being a potential candidate for biological evaluations. The results obtained allowed us to observe that virtual detection based on substructures using a molecular docking approach and molecular dynamics simulation is a useful method for the identification of biologically important compounds.

Virtual detection based on ligands and molecular dynamics of benzimidazole derivatives with potential inhibitory activity of Trypanosoma cruzi triosaphosphate isomerase

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