Complexes of N-hydroxyethyl-N-benzimidazolylmethylethylenediaminediacetic acid with group 12 metals and vanadium-Synthesis, structure and bioactivity of the vanadium complex.
Four new complexes of group 12 metals [Zn(II), Cd(II) and Hg(II)], along with vanadyl bound to the ligand N-hydroxyethyl-N-benzimidazolylmethylethylenediaminediacetic acid, have been synthesized and characterized. The structure of the complexes with Zn(II), Hg(II) and V(IV) was determined by X-ray structural analysis. In all observed cases, the symmetry of these complexes was found to be distorted octahedral. The inhibition of protein tyrosine phosphatase 1B by the vanadium(IV) complex was demonstrated. The cytotoxicity of the vanadium(IV) complex was tested in vitro against three cancer cell lines, with a comparison of the activity of the free ligand and of vanadyl acetylacetonate and sodium orthovanadate. The IC50 values of the complex were in the range of 9 to 21μM. Remarkably, cytotoxic potency in the multidrug-resistant non-small cell lung cancer cell line A549 was at least as high as in the broadly chemosensitive ovarian teratocarcinoma cell line CH1(PA-1).
Institut für Biophysikalische Chemie, Fakultät für Chemie, Universität Wien, Althanstr. 14, A-1090 Wien, Austria; Department of Chemical Theory of Drugs, Faculty of Pharmacy, Comenius University, Kalinciakova 8, SK-832 32 Bratislava, Slovakia.
Ladislav
L
Habala
Institut für Anorganische Chemie, Fakultät für Chemie, Universität Wien, Althanstr. 14, A-1090 Wien, Austria.
Caroline
C
Bartel
Institut für Mineralogie und Kristallographie, Universität Wien, Althanstr. 14, A-1090 Wien, Austria.
Gerald
G
Giester
Institut für Anorganische Chemie, Fakultät für Chemie, Universität Wien, Althanstr. 14, A-1090 Wien, Austria.
Michael A
MA
Jakupec
Institut für Anorganische Chemie, Fakultät für Chemie, Universität Wien, Althanstr. 14, A-1090 Wien, Austria.
Bernhard K
BK
Keppler
Institut für Biophysikalische Chemie, Fakultät für Chemie, Universität Wien, Althanstr. 14, A-1090 Wien, Austria. Electronic address: annette.rompel@univie.ac.at.
Annette
A
Rompel
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001562:Benzimidazoles / Q000737:chemistry* / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D056831:Coordination Complexes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D005029:Ethylenediamines / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000037:antagonists & inhibitors; D017968:Vanadium Compounds / Q000737:chemistry*
D000970:Antineoplastic Agents; D001562:Benzimidazoles; D056831:Coordination Complexes; D005029:Ethylenediamines; D017968:Vanadium Compounds; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1
Anticancer activity; Cytotoxicity; Heavy metals; Metal complex; Vanadium(IV) complex