Synthesis and characterization of hydrazones and their vanadium complexes, and study of their possible pharmacological applications

Resumo

The lack of treatment for various diseases, drug resistance, and harmful side effects of certain compounds have made the search for new drugs a priority. Hydrazide-hydrazones, organic compounds with diverse biological properties, may serve as ligands in coordination compounds. Vanadium compounds have also shown potential in designing new metallodrugs with antibacterial, antiviral, and antitumoral activities. This thesis was aimed to evaluate the relationship between chemical structure and biological properties of several hydrazide-hydrazones ligands and vanadium complexes. In particular, two groups of hydrazide-hydrazone compounds derived from pyridoxal and from 2,6-diformyl-4-methylphenol with seven different aromatic rings as substituents and their corresponding vanadium complexes were synthetized and characterized by a number of analytical methodologies. Besides, the interaction of these compounds with biomolecules, specifically DNA and albumin, and their cytotoxic potency (IC50 and morphological changes) were also determined on lung A549 cells. Binding with DNA and albumin were confirmed in almost all cases. The tested compounds induced alterations in cell morphology and most compounds had an IC50 higher than 250 μM after 24 hours of treatment. These results constitute the first steps in the development of vanadium-based metallodrugs eventually valuable for further biomedical applications.