Water-Soluble Dioxidovanadium(V) Complexes of Aroylhydrazones: DNA/BSA Interactions, Hydrophobicity, and Cell-Selective Anticancer Potential

Five new anionic aqueous dioxidovanadium(V) complexes, [{VO 2 L 1,2 }A(H 2 O) n ] α ( 1 – 5 ), with the aroylhydrazone ligands pyridine-4-carboxylic acid (3-ethoxy-2-hydroxybenzylidene)hydrazide (H 2 L 1 ) and furan-2-carboxylic acid (3-ethoxy-2-hydroxybenzylidene)hydrazide (H 2 L 2 ) incorporating different alkali metals (A = Na +, K +, Cs + ) as countercation were synthesized and characterized by various physicochemical techniques. The solution-phase stabilities of 1 – 5 were determined by time-dependent NMR and UV–vis, and also the octanol/water partition coefficients were obtained by spectroscopic techniques. X-ray crystallography of 2 – 4 confirmed the presence of vanadium(V) centers coordinated by two cis -oxido-O atoms and the O, N, and O atoms of a dianionic tridentate ligand. To evaluate the biological behavior, all complexes were screened for their DNA/protein binding propensity through spectroscopic experiments. Finally, a cytotoxicity study of 1 – 5 was performed against colon (HT-29), breast (MCF-7), and cervical (HeLa) cancer cell lines and a noncancerous NIH-3T3 cell line. The cytotoxicity was cell-selective, being more active against HT-29 than against other cells. In addition, the role of hydrophobicity in the cytotoxicity was explained in that an optimal hydrophobicity is essential for high cytotoxicity. Moreover, the results of wound-healing assays indicated antimigration in case of HT-29 cells. Remarkably, 1 with an IC 50 value of 5.42 ± 0.15 μM showed greater activity in comparison to cisplatin against the HT-29 cell line.