New chemotypes as <i>Trypanosoma cruzi</i> triosephosphate isomerase inhibitors: a deeper insight into the mechanism of inhibition

Abstract

At low micromolar concentrations, the compounds induce highly selective irreversible inactivation of parasitic TIM. The molecular docking simulations indicate that the phenazine derivative likely interferes with the association of the two monomers of the dimeric enzyme by locating at the dimer interface, while 1,2,6-thiadiazine could act as an inhibitor binding to a region surrounding Cys-118.