Biological and physical properties of ruthenium complexes

Ruthenium(III) complexes are considered as potential antineoplastic compounds of increasing interest. Morever, these compounds exert an important antimetastatic activity that is rarely observed in other antitumor drugs. Although it was suggested that the main target for ruthenium compounds is DNA, the mechanism of action of these compounds is still largely unknown and alternative biological targets have been proposed. Coupling of ruthenium- dmso complexes exhibiting potential antitumor properties to semihiosemicarbazone moieties will result in the synthesis of new potential antitumor complexes, that will be followed by examination of their biological and antitumor activity. The aim of this study is to examine in vitro effects of these new compounds on cell proliferation. To better establish the nature of action it is noteworthy to investigate the interaction, i.e. nature of damage that ruthenium complexes infer on DNA and to determine if DNA may be target for this family of drug. Aditionally, the interaction of other ruthenium antitumor complexes with DNA could be also investigated through a number of spectroscopic and molecular biology techniques. To get some insight into the possible mechanism of action of complex(es) their solution behaviour and reactivity towards proteins will be investigated through various physico-chemical techniques including spectrophotometry, circular dicroism, gel shift analysis and restriction enzyme inhibition. It is of interest to consider the interactions of complexes with plasma proteins, in particular with serum albumin, as these proteins represent the first possible targets for ruthenium compounds after intravenous administration. Detailed knowledge of the interactions of ruthenium antitumor complexes with plasma proteins is of concern because binding of proteins might result in modification, or even loss, of the biological properties of the starting compound. Attempts will be made to elucidate the molecular mechanism of binding to proteins and to characterize the resulting adducts.