PHYSICOCHEMICAL STUDY, CRYSTAL STRUCTURE AND ANTITUMORAL ACTIVITY OF A NOVEL VANADIUM(V) COMPLEX WITH AN ISONIAZID-DERIVED HYDRAZONE LIGAND

ANA C. GONZÁLEZ-BARÓ; VERÓNICA FERRARESI CUROTTO; JACKSON A. L. C. RESENDE; FLÁVIA C. S. DE PAULA; ELENE C. PEREIRA-MAIA; NICOLÁS A. REY

Punta del Este

Simposio; XII Symposium on Metal Ions in Biology and Medicine; 2013

The combination of isoniazid (a well known antituberculous agent) with o-vanillin leads to the formation of a stable and active hydrazone, INHOVA1. The interaction of this compound with vanadium was studied in an attempt to obtain metal complexes of therapeutic interest. The complex was prepared from ethanolic solutions of INHOVA and VOCl2 in a 1:1 molar ratio and obtained in the hydrochloride form, with protonation of the pyridine N atom. It crystalizes in the monoclinic system, space group P21/c. INHOVA acts as a tridentate ligand and the distorted coordination environment is completed by an oxo ligand, a disordered ethoxide and a water molecule.The optimized geometry of the complex, the vibrational analysis and the  vertical electronic transitions were obtained within the context of the DFT. Basis sets of triple-ζ quality were used. Solvent effects were included through the IEF-PCM. The IR spectrum of the solid and the UV-Vis spectra in DMSO and ethanol  were compared with those of the free ligand. The assignments were  accomplished with the help of theoretical calculations. Electronic spectra were similar in both solvents, in accordance with theoretical predictions. The bands could be assigned to intraligand and charge transfer transitions. Theredox behaviors of the complex and the ligand were studied by cyclic voltammetry in the same solvents. Several irreversible oxidation and  reduction processes involving the metal center and the coordinated ligand were observed. Both INHOVA and the complex showed activity against the chronic  myelogenous leukemia K562 cell line in a concentration-dependent manner. The IC50 (concentration required to inhibit 50% of cellular growth) values obtained were, respectively, 36.46 ± 4.13 and 28.80 ± 3.48 µmol L-1.[1] Ana C. González-Baró, Reinaldo Pis-Diez, Beatriz S. Parajón-Costa, Nicolás A. Rey; Spectroscopic and theoretical study of the o-vanillin hydrazone of the mycobactericidal drug isoniazid. J .Mol. Struct. 2012, 1007, 95?101.