Effects of some ruthenium chelates on MCa mammary carcinoma and on TLX5 lymphoma in mice.

A group of four Ruthenium chelates of the mixed hard/soft N-S donor ligands 2-formylpyridine (4-H/4-phenyl)thiosemicarbazone has been studied in the experimental models of MCa mammary carcinoma and TLX5 lymphoma in the CBA mouse. Although all the four tested complexes, bis-[2-formylpyridine(4- phenyl)thiosemicarbazone]ruthenium(II)chloride]Ru(L1)(L1H)Cl, 1], [2-formylpyridine(4-phenyl)thiosemicarbazone]ruthenium(II)-mu- trichloro chloro(imidazole)ruthenium(III)monomethanolate [Ru2(L1)(imz)Cl4.CH3OH, 9]. [2-formylpyridine(4-phenyl)thiosemicarbazone]dichloroimidazoler uthenium(II) [Ru(L1H)(imz)Cl2,10] and bis[2- formylpyridinethiosemicarbazone]ruthenium(II) perchlorate, dihydrate [Ru(L)(LH)ClO4.2H2O, 16], reduced the formation of lung metastases at the same extent only compound 1 caused parallel inhibition of the growth of the primary tumor. The chemical nature of the tested compounds seems to determine the nature of the antitumor effects and the bis-chelates are found to be endowed with greater cytotoxic properties towards primary tumor than the monochelates. This opens up a very interesting point, whether it is the presence of two chelate rings around the Ruthenium(II)/(III) acceptor centre or the increase in the number of the soft (S) donor centers that generates greater cytotoxic properties in the corresponding ruthenium complexes. As far as the reduction of the metastasis formation is concerned, it appears that among the four Ruthenium chelates tested, it is possible to identify structures capable of controlling the spread of tumor to the lungs in the absence of significant cytotoxicity for tumor cells. This finding appears of importance in that it indicates the possibility of a specific mechanism of interaction with cells of the metastatic tumor. In this context it appears necessary to investigate other congeners of this "family" with more sulfur donor sites and particularly those with better water solubility.