| Abstract |
In Latin America Chagas disease is an endemic illness caused by the parasite Trypanosoma cruzi (T. cruzi), killing more people than any other parasitic disease. Current chemotherapies are old and inadequate, thus the development of efficient ones is urgently needed. Vanadium-based complexes have been shown to be a promising approach both against parasitic diseases and cancer and this study aims to achieve significant advances in the pursue of effective compounds. Heteroleptic vanadium complexes of Schiff bases and polypyridine compounds were prepared and their stability in solution evaluated by EPR (Electronic Paramagnetic Resonance) and NMR spectroscopy. Their in vitro activities were evaluated against T. cruzi and a set of cells lines representative of human cancer conditions, namely ovarian, breast and prostate cancer. In T. cruzi, most of the complexes depicted IC50 values in the low mu M range, induced changes of mitochondrial membrane potential and apoptosis. In cancer cells, complexes showed good to moderate activity and in metastatic cells (prostate PC3), some complexes inhibited the migratory ability, this suggesting that they display antimetastatic potential. Interestingly, complex 5 seemed to have a dual effect being the most cytotoxic complex on all cancer cells and also the most active anti-T-cruzi compound of the series. Globally the complexes showed promising anticancer and anti T. cruzi activities and also displayed some characteristics indicating they are worth to be further explored as antimetastatic drugs. |
