Relationship between structure and cytotoxicity of vanadium and molybdenum complexes with pyridoxal derived ligands

In this work four vanadium complexes (compounds 1, 2, 3 and 4) and one molybdenum complex (compound 5) with hydrazone ligands derived from pyridoxal were synthesized and characterized. All compounds are mononuclear species, two of them (compounds 3 and 5) are dioxide complexes and the other three (compounds 1, 2 and 4) monoxide complexes. The vanadium atom of the compound 3 is five-coordinated and all the other compounds have a six coordinated environment polyhedron. The poses for the potential intercalation of the compounds 2 and 3 with DNA were obtained by using AutoDock software. Optimizations were also performed at PM6-D3H4 semi-empirical level whereas the study of the nature of the interaction was carried out by means of the Energy Decomposition Analysis and the Non-Covalent Interaction index by using in both cases Density Functional Theory computations. The cytotoxicity in lung cancer cells (A549 cell line) of all the compounds was also evaluated. After 24 h of treatment, vanadium complexes showed high values of IC₅₀, between 419.93 ± 22.58 and 685.88 ± 46.55 μM. After 48 h, the results showed that the compound 3 had the lowest IC₅₀ value, 65.32 ± 9.95 μM, and the compound 2 the highest value, 375.28 ± 32.09 μM. The molybdenum complex showed the lowest IC₅₀ value at 48 h (11.22 ± 1.34 μM). The toxicity of the compounds 3, 4 and 5 was tested in vivo, using zebrafish model, and the molybdenum complex showed higher toxic effects than the studied vanadium complexes.