title: Highly Effective and Hydrolytically Stable Vanadium(V) Amino Phenolato Antitumor Agents.
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. In vivo 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.
authors.affiliation: Institute of Chemistry, the Hebrew University of Jerusalem , Jerusalem 9190404, Israel.
authors.forename: Lilia
authors.initials: L
authors.lastname: Reytman
authors.affiliation: Department of Cell and Developmental Biology, Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem , Jerusalem 9190401, Israel.
authors.forename: Ori
authors.initials: O
authors.lastname: Braitbard
authors.affiliation: Department of Cell and Developmental Biology, Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem , Jerusalem 9190401, Israel.
authors.forename: Jacob
authors.initials: J
authors.lastname: Hochman
authors.affiliation: Institute of Chemistry, the Hebrew University of Jerusalem , Jerusalem 9190404, Israel.
authors.forename: Edit Y
authors.initials: EY
authors.lastname: Tshuva
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D006868:Hydrolysis; D017968:Vanadium Compounds / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D017968:Vanadium Compounds