Antiproliferative activity of heterometallic sodium and potassium-dioxidovanadium(V) polymers

The syntheses of the heterometallic sodium and potassium-dioxidovanadium 2D polymers, [NaVO₂(1κNOO';2κO"-L)(H₂O)]_n(1) and [KVO₂(1κNOO';2κO';3κO"-L)(EtOH)]_n(2) (where the κ notation indicates the coordinating atoms of the polydentate ligand L) derived from (3,5-di-tert-butyl-2-hydroxybenzylidene)-2-hydroxybenzohydrazide (H₂L) are reported. The polymers were characterized by IR, NMR, elemental analysis and single crystal X-ray diffraction analysis. The antiproliferative potential of 1 and 2 was examined towards four human cancer cell lines (ovarian carcinoma, A2780, colorectal carcinoma, HCT116, prostate carcinoma, PC3 and breast adenocarcinoma, MCF-7cell lines) and normal human fibroblasts. Complex 1 and 2 showed the highest cytotoxic activity against A2780 cell line (IC₅₀ 8.2 and 11.3 μM, respectively) with 1 > 2 and an IC₅₀ in the same range as cisplatin (IC₅₀ 3.4 μM; obtained in the same experimental conditions) but, interestingly, with no cytotoxicity to healthy human fibroblasts for concentrations up to 75 μM. This high cytotoxicity of 1 in ovarian cancer cells and its low cytotoxicity in healthy cells demonstrates its potential for further biological studies. Our results suggest that both complexes induce ovarian carcinoma cell death via apoptosis and autophagy, but autophagy is the main biological cause of the reduction of viability observed and that ROS (reactive oxygen species) may play an important role in triggering cell death.