Identification of descriptors for structure-activity relationship in ruthenium (II) mixed compounds with antiparasitic activity

Herein is presented the synthesis, characterization, electrochemical studies, DFT calculations and in vitro evaluation of amoebicidal activity in trophozoites of Entamoeba histolytica of twenty ruthenium (II) mixed compounds with general formulae: (Ru(pdtoXE-E)]Cl-x (E-E bidentate, either neutral or negatively charged ligands). For compounds under study, O-O, N-O and N-N auxiliary donor ligands demonstrate to have a crucial impact on the electronic properties and that it is possible to modulate the antiparasitic activity. Among analyzed complexes, only four present a better performance compared to typically used metronidazole drug (IC50 < 6.80 mu mol/L) to treat amebiasis disease. For studied compounds, structure-activity relationships are strongly determined by either the redox potential (E-1/2) of Ru-II/Ru-III and calculated molar volume (V) of the complexes. (C) 2020 Elsevier Masson SAS. All rights reserved.