Abstract
625
Lipophilic dithiocarbamates have been shown to induce metal uptake into cells, often generating an apoptotic response. We have previously demonstrated that Cu(II) and Zn(II) complexes of pyrollidinedithiocarbamate show high anti-melanoma activity which is enhanced under high oxygen conditions, and that they have much lower toxicity against normal cells. Simple structure/activity relationship of the N-substituted Zn dithiocarbamates will be discussed. We have also demonstrated that the alcohol-abuse deterrent disulfiram (DSF) has a highly selective, Cu(II)-dependent toxicity against melanoma in culture. The alcohol-abuse deterrent activity of DSF is thought to be due to S-oxygenation in vivo, which enhances its inhibition of the enzyme aldehyde dehydrogenase. We have found that partial S-oxygenation of Zn dithiocarbamates enhance their anti-melanoma activity. This work has lead to identification of other thione chelators with high anti-melanoma activity. (Sponsored by Dr. Bradley Monk)
[Proc Amer Assoc Cancer Res, Volume 46, 2005]
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