Metal complex derivatives of bis(pyrazol-1-yl)methane ligands: synthesis, characterization and anti-Trypanosoma cruzi activity

In this work, the synthesis and characterization of seven complexes (1-7) was performed with Zn(II), Cu(II), Co(II) and Ni(II) transition metals and ligands derived from bis(3,5-dimethylpyrazol-1-yl)methane (bdmpzm) and bis(3,5-dimethyl-4-nitro-1H-pyrazolyl)methane (L). The complexes were obtained in high yields, isolated as air-stable solids and characterized by physicochemical and spectroscopic methods. The structures of L and complex 1 were determined by single-crystal X-ray diffraction analysis. The complexes and their respective ligands were evaluated against epimastigotes of Trypanosoma cruzi strains. An increase in the activity of the complexes was observed compared to the free ligands. Greater activities were found for Co(II) complexes than for Cu(II), Ni(II) and Zn(II) complexes. Additionally, complexes 3 and 9 had little effect on erythrocytes, indicating that they are non-toxic. The results obtained in mitochondrial membrane potential analyses suggest a possible mechanism by which complex 3 has a trypanocidal effect through the induction of oxidative stress. The results could provide an interesting contribution to the further design of active complexes against T. cruzi.Graphical abstractSynthesis and structural characterization of new complexes with zinc(II), copper(II), cobalt(II) and nickel(II) transition metals derived from bis(pyrazol-1-yl)methane ligands. The cobalt(II) complexes have high activity against epimastigotes from Trypanosoma cruzi strains and are not toxic.