Highly Effective and Hydrolytically Stable Vanadium(V)
Amino Phenolato Antitumor Agents
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Abstract
Vanadium(V) oxo complexes
with no labile ligands, including six
octahedral complexes with pentadentate diaminotris(phenolato) ligands
and one pentacoordinate complex with a tetradentate aminotris(phenolato)
ligand, were synthesized in high yields. All octahedral complexes
demonstrated high hydrolytic stability with no signs of decomposition
after days in the presence of water, whereas the pentacoordinate complex
decomposed within minutes to release the free ligand, demonstrating
the marked impact of coordination number and geometry on the complex
electrophilicity. All complexes showed marked cytotoxicity toward
human colon HT-29 and ovarian OVCAR-3 cells. In particular, the octahedral
complexes exhibited especially high activity, higher than that of
cisplatin by up to 200-fold. Selected complexes demonstrated similarly
high activity also toward the A2780 and the A2780cis cisplatin-resistant
line. High cytotoxicity was also recorded after prolonged incubation
in a DMSO solution at 4 and 37 °C temperatures and in biological
medium. <i>In vivo</i> studies pointed to high efficacy
in reducing tumor size, where no clinical signs of toxicity were detected
in the treated mice. These results overall indicate high potential
of the tested compounds as antitumor agents