Cytotoxic Activity of Gd(III)‐ and Dy(III)‐Complexes

Abstract

The complexes of gadolinium(III) and dysprosium(III) were synthesized by reaction of the respective inorganic salts with 3,5-pyrazoledicarboxylic acid in amounts equal to metal to ligand molar ratio of 1 : 2. The structures of the final complexes were determined by means of spectral and elemental analyses. To help further the binding mode elucidation in the new Gd(III)- and Dy(III)-complexes of H(3)pdc, detailed vibrational analysis was performed on the basis of comparison of experimental vibrational spectra of the ligand and its Ln(III)-complexes using data theoretically predicted by us earlier, as well as data from the literature about related compounds. Significant differences in the IR and Raman spectra of the complexes were observed as compared to the spectra of the ligand. The ligand and the complexes were tested for their cytotoxic activities on the chronic myeloid leukemia-derived K-562, overexpressing the BCR-ABL fusion protein and the non-Hodgkin lymphoma-derived DOHH-2, characterized by a re-expression of the anti-apoptotic protein bcl-2 cell lines. The results obtained indicate that the tested compounds exerted a considerable cytotoxic activity upon the evaluated cell lines in a concentration-dependent manner, which enabled the construction of dose-response curves and the calculation of the corresponding IC(50) values. The inorganic salts exerted a very weak cytotoxic effect on these cells. This is in contrast to the lanthanide complexes, which exhibited potent cytotoxic activity, even more than the activity of cisplatin towards K-562 and DOHH-2 cell lines.

Lanthanide luminescence for functional materials and bio-sciences

“…382 Lanthanide ions have also anticoagulant properties but their main therapeutic applications lie presently in the radioactive treatment of cancers. The toxicity of free lanthanide ions vary considerably, IC 50 being reported between 1 and 1000 mM for Gd III for instance, [383][384][385] while under given experimental conditions they even enhance cell proliferation. 386 Gadolinium chelates are ubiquitous contrast agents for magnetic resonance imaging [387][388][389] and despite some recently reported problems with one class of compounds 390 they are well tolerated and considered as being harmless.…”

Metal Drugs and the Anticancer Immune Response

“…There are few reports on the lanthanide gadolinium (Gd) as metal-component of anticancer agents. Evidence for the potential of Gd as an anticancer metal agent arises for instance from a report on Gd­(III) complexes of coumarin-3-carboxylic acid, which have been tested for their antiproliferative activity in CML cells in vitro. , Information on immunological aspects of compounds containing Gd are lacking, owing to the yet limited existence of in vivo experiments or appropriate ex vivo cocultures aimed at characterizing cancer-immune cell interactions.…”