Interactions of dinuclear transition metal complexes with amino acids, nucleotides, and DNA

In the 1960's the discovery that cis-platin was a potent antitumor agent paved the way for the use of metal-based drugs in modern chemotherapeutic applications. The severe side effects exhibited by this drug have led to the investigation of new types of metal-based compounds as potential antitumor agents. Dinuclear transition metal compounds are among these compounds. These have been found to exhibit carcinostatic activity, and like cis-platin, are inhibitors of DNA replication. In order to understand potential mechanisms which could lead to the development of more effective treatments, the interactions of these antitumor agents with cellular molecules must be studied. Reactions of dinuclear compounds with thiol-dependent enzymes and/or DNA bases leading to distortions, may be responsible for their activity. In order to develop an understanding of the in vivo interactions these dinuclear compounds may undergo, reactions with cellular components were studied. Presented here are the results from the studies of dinuclear transition metal compounds with the amino acids methionine, cysteine, and glutathione along with the nucleotides adenosine, guanosine, and DNA.