"Platinum-pyrimidine blues" and related complexes: a new class of potent antitumor agents

Abstract

The diaquo species of cis-dichlorodiammineplatinum (II) reacts with pyrimidines and substituted pyrimidines to form very soluble, deep blue complexes. These are believed to consist of mainly monomeric species containing one pyrimidine moiety liganded to each platinum. The structures of the complexes are largely uncertain at this time. We describe the methods of synthesis and characterization of approximately 70 such complexes, with a suggested classification scheme, incluse complexes show superior activity against the ascites Sarcoma 180 tumor in Swiss mice when compared to cis-dichlorodiammineplatinum (II). Initial screening test results and dose schedule-dependency results indicate we can achieve 100% cures in this tumor-host system. Activity is also shown against the Rauscher leukemia, Ehrlich ascites, and ADJ/PC6A tumors. Microscopic histopathologic studies of resulting kidney lesions show that the "platinum-uracil blue" complex causes only minor focal damage to the proximal convoluted tubules at a therapeutic dose level, rather than the generalized degenerative changes so prominent and dose limiting noted with cis-dichlorodiammineplatinum (II).