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 li gands 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-form yplyridine(4-phenyl) emicarbazone]ruthenium(II)chlo-ride[Ru(L1)(L1H)Cl , 1], enyl)thiosemi-carbazone]ruthenium(II)-mu-trichloro chloro(imidaz ole)rutheni um(III)monomethanolate [Ru2(L1)(imz)Cl4.CH3OH, 9], )thiose micarbazone]dichloroimida-zoleruthenium(II) [Ru(L1H)(imz)Cl2, 10] and is[2-formylpyridinethiosemicarbazone]ruthentum(II) perchlorate, dihydr ate [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 compoun ds seems to determine the nature of the antitumor effects and the bis- chelates are found to be endowed with greater cytotoxic properties tow ards primary tumor than the monochelates. This opens up a very interes ting 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 capab le of controlling the spread of tumor to the lungs in the absence of s ignificant cytotoxicity for tumor cells. This finding appears of impor tance in that it indicates the possibility of a specific mechanism of interaction with cells of the metastatic tumor. In this context it app ears necessary to investigate other congeners of this <<family>> with more sulfur donor sites and particularly those with better water solub ility.