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J Med Chem. 2005 Dec 15;48(25):7925-31.

Antitumoral activity of non-platinum xanthate complexes.

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German Cancer Research Centre, Department D060, Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany.


To establish structure-activity relationships, derivatives of bis(O-alkyldithiocarbonato)platinum(II) complexes were analyzed. Eighteen bis(O-alkyldithiocarbonato) metal complexes were synthesized, and their cytotoxic activity on two human cancer cell lines was compared with the corresponding platinum bis(O-alkyldithiocarbonato) complexes and cisplatin. Complexes were synthesized with palladium, gold, nickel, copper, rhodium, and bismuth. Palladium and bismuth complexes were found to display significant cytotoxic activity. Palladium complexes were most active with up to 10-fold lower IC50 values as compared with the corresponding platinum complexes. The other complexes were only poorly active. Palladium, bismuth, and nickel complexes were more active at pH 6.8 than at pH 7.4. This difference in activity was most pronounced with palladium complexes. A pH of 6.8 and lower has been frequently found in solid tumors. Drugs with such pH dependent activity are supposed to have an improved therapeutic index as compared to drugs that are active irrespective of pH.

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