Design of vanadium mixed-ligand complexes as potential anti-protozoa agents

In the search for new therapeutic tools against Chagas’ disease (American Trypanosomiasis) four novel mixed-ligand vanadyl complexes, [VIVO(L2-2H)(L1)], including a bidentate polypyridyl DNA intercalator (L1) and a tridentate salycylaldehyde semicarbazone derivative (L2) as ligands were synthesized, characterized by a combination of techniques, and in vitro evaluated. EPR suggest a distorted octahedral geometry with the tridentate semicarbazone occupying three equatorial positions and the polypyridyl ligand coordinated in an equatorial/axial mode. Both complexes including dipyrido[3,2-a: 2′,3′-c]phenazine (dppz) as polypyridyl coligand showed IC50 values in the μM range against Dm28c strain (epimastigotes) of Trypanosoma cruzi, causative agent of the disease, being as active as the anti-trypanosomal reference drug Nifurtimox. To get an insight into the trypanocidal mechanism of action of these compounds, DNA was evaluated as a potential parasite target and EPR, and 51V NMR experiments were also carried out upon aging aerated solutions of the complexes. Data obtained by electrophoretic analysis suggest that the mechanism of action of these complexes could include DNA interactions.