Vanadium(IV/V) complexes of Triapine and related thiosemicarbazones: Synthesis, solution equilibrium and bioactivity.
The stoichiometry and thermodynamic stability of vanadium(IV/V) complexes of Triapine and two related α(N)-heterocyclic thiosemicarbazones (TSCs) with potential antitumor activity have been determined by pH-potentiometry, EPR and (51)V NMR spectroscopy in 30% (w/w) dimethyl sulfoxide/water solvent mixtures. In all cases, mono-ligand complexes in different protonation states were identified. Dimethylation of the terminal amino group resulted in the formation of vanadium(IV/V) complexes with considerably higher stability. Three of the most stable complexes were also synthesized in solid state and comprehensively characterized. The biological evaluation of the synthesized vanadium complexes in comparison to the metal-free ligands in different human cancer cell lines revealed only minimal influence of the metal ion. Thus, in addition the coordination ability of salicylaldehyde thiosemicarbazone (STSC) to vanadium(IV/V) ions was investigated. The exchange of the pyridine nitrogen of the α(N)-heterocyclic TSCs to a phenolate oxygen in STSC significantly increased the stability of the complexes in solution. Finally, this also resulted in increased cytotoxicity activity of a vanadium(V) complex of STSC compared to the metal-free ligand.
University of Vienna, Institute of Inorganic Chemistry, Währinger Strasse 42, A-1090 Vienna, Austria; Research Platform "Translational Cancer Therapy Research" University of Vienna, Waehringer Strasse 42, A-1090 Vienna, Austria. Electronic address: christian.kowol@univie.ac.at.
Christian R
CR
Kowol
Institute of Organic Chemistry, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Magyar Tudósok körútja 2, H-1117 Budapest, Hungary.
Nóra V
NV
Nagy
Department of Inorganic and Analytical Chemistry, University of Szeged, H-6720 Szeged, Hungary.
Tamás
T
Jakusch
University of Vienna, Institute of Inorganic Chemistry, Währinger Strasse 42, A-1090 Vienna, Austria.
Alexander
A
Roller
Research Platform "Translational Cancer Therapy Research" University of Vienna, Waehringer Strasse 42, A-1090 Vienna, Austria; Institute of Cancer Research and Comprehensive Cancer Center, Medical University of Vienna, Borschkegasse 8a, A-1090 Vienna, Austria.
Petra
P
Heffeter
University of Vienna, Institute of Inorganic Chemistry, Währinger Strasse 42, A-1090 Vienna, Austria; Research Platform "Translational Cancer Therapy Research" University of Vienna, Waehringer Strasse 42, A-1090 Vienna, Austria.
Bernhard K
BK
Keppler
Department of Inorganic and Analytical Chemistry, University of Szeged, H-6720 Szeged, Hungary. Electronic address: enyedy@chem.u-szeged.hu.
Éva A
ÉA
Enyedy
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D045744:Cell Line, Tumor; D006801:Humans; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D011725:Pyridines / Q000737:chemistry*; D013882:Thiosemicarbazones / Q000737:chemistry*; D014639:Vanadium / Q000737:chemistry*
D000970:Antineoplastic Agents; D009942:Organometallic Compounds; D011725:Pyridines; D013882:Thiosemicarbazones; D014639:Vanadium; C078157:3-aminopyridine-2-carboxaldehyde thiosemicarbazone
Cytotoxicity; EPR spectroscopy; Equilibria; Stability constants; X-ray crystal structure