Characterization and in vitro Cytotoxicity Testing of Ethanolamine-derived Cadmium Chelating Agents

• Published in: Biometals 2007-02, Vol.20 (1), p.61-72
• Main Authors: Zhukalin, Mikhail, Blanksma, Megan K, Silva, T. Dimitri, Suyehira, Samuel W, Harvey, Wendy A, Heggland, Sara J, Craig, Peter R
• Format: Article
• Language: English
• Subjects: Cadmium; Cadmium - chemistry; Cadmium Chloride - pharmacology; Cell Adhesion - drug effects; Cell Line, Tumor; Cell Survival - drug effects; Chelating agents; Chelating Agents - chemical synthesis; Chelating Agents - chemistry; Chelating Agents - pharmacology; chelation; Chemical composition; Cytotoxicity; dithiocarbamate; Dose-Response Relationship, Drug; Ethanolamine - chemistry; Humans; in vitro testing; Molecular Structure; Thiocarbamates - chemistry; xanthate
• ISSN: 0966-0844; 1572-8773
• DOI: 10.1007/s10534-006-9015-1

We have synthesized and characterized the new cadmium chelating agent potassium bis(2-hydroxyethyl)aminoethyldithiocarbonate hemihydrate, K[bhexan] · 0.5H₂O (2), that is structurally related to the known effective in vivo cadmium chelating agent potassium bis(2-hydroxyethyl)dithiocarbamate, K[bhedtc] (1). The corresponding cadmium complex of 2 differs from di(bis(2-hydroxyethyl)dithiocarbamato)cadmium(II), Cd(bhedtc)₂ (3), in that the insoluble compound exhibits an elemental composition consistent with a cadmium:ligand ratio of 2:1. The cytotoxicity of the 1-3 was investigated using the human osteoblast-like cell line, Saos-2. Compounds 1 or 2 did not affect cell adherence or cell viability in the 100-500 μM concentration range studied, whereas 3 resulted in a concentration-dependent increase in loss of cell adherence and decrease in cell viability. Overall, the results of the loss of cell adherence, trypan blue exclusion and MTT assays showed that administration of 3 (cadmium complex of 1) resulted in cytotoxicity lower than that of cadmium chloride, but higher than that of the chelator 1 alone. The effect of simultaneous addition of cadmium chloride and 1 or 2 on cell viability was also assessed using the MTT assay. For the 100 μM cadmium chloride experiments, cell viability comparable to control cells was achieved for both 1 and 2 in the 100-500 μM concentration range studied. Cell viability comparable to control cells was achieved for 1 but not 2 in the 100-500 μM concentration range studied for the 200 μM cadmium chloride experiments. Thus 1 appears more effective than 2 in the ability to mediate the cytotoxic effects of cadmium in vitro upon concomitant administration.