Coordination metal complexes of Rh(I), Ir(I) and Ru(II): recent advances on antimetastatic activity on solid mouse tumors

Following pioneering observations on the mouse Ehrlich ascites carcinoma, the result of cooperation between the Institutes of Chemistry and Pharmacology of the University of Trieste, more recent studies have characterized some aspects of the antimetastatic properties of coordination metal complexes other than platinum compounds. The compounds examined, rhodium(I) and iridium(I) derivatives of the type [Mchel(LL)]+/o (chel= pyridinalimine (NNR), acetylacetonate; LL= 1,5-hexadiene, 1,5-cyclooctadiene, norbornadiene), both with a square-planar structure, and an octahedral ruthenium(II) derivative RuCl2(dimethylsulfoxide)4 were tested using the solid metastasizing tumor of the mouse, Lewis lung carcinoma. The conclusions which can be drawn from the resulting data concern the role of the metal, of the leaving group and of the non-leaving group as well. It was found that the organometallic complexes of Rh(I) are more active than those of Ir(I); within the Rh(I) derivatives of the type [Rh(I)COD(NNR)]+Cl- (RCH3, C2H5, iC3H7), the higher the hydrosolubility, the higher is the antitumor and particularly the antimetastatic effect; as far as the diolefinic ligands are concerned, the higher the chelating effect the higher are the antimetastatic properties of the resulting compound. Separate conclusions can be made for the Ru(II) derivative. Comparison of its antimetastatic effects with those of cis-dichlorodiammineplatinum(II) (cisplatin) using three solid mouse tumors, clearly shows a better therapeutic index for the former, suggesting that within this class of compounds it is conceivable to obtain derivatives with an antineoplastic activity comparable to or even higher than that of cisplatin.