2-Amino diphenylsulfides as inhibitors of trypanothione reductase: modification of the side chain Original Research Article

A molecular modeling study meant to detect pharmacophore-like patterns in the active site of trypanothione reductase (TR) offered hints about the opportunity of synthesizing and testing diphenylsulfide derivatives with prolonged or branched polyamino side chains as putative TR inhibitors. The inhibition results within the synthesized series confirmed the main working hypothesis inspired by the molecular modeling study. The different compounds were tested in vitro on the enzyme and on Trypanosoma cruzi and Trypanosoma brucei trypomastigotes as well as in vivo in infected mice.