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Antitumor Action of Two Rhodium and Ruthenium Complexes in Comparison with cis-Diamminedichloroplatinum(II)¹

Istituto di Farmacologia [T.G., G.S., G.B.] and Istituto di Chimica, [G.M., G.Z.], Università di Trieste, I-34100 Trieste, Italy

Two organometallic complexes, acetylacetonate-1,5-cyclooctadienerhodium(I) ([RhacacCOD]⁰) and cis-dichlorotetrakisdimethylsulfoxide ruthenium(II) ([cis-Ru(II)(DMSO)₄-Cl₂]⁰), have been examined for antitumor activity. Rhacac-COD had an activity comparable with that of cis-diamminedichloroplatinum(II) (cis-PDD) against Ehrlich ascites carcinoma, yielding 100% cures at two dosages, whereas the comparative activity of [cis-Ru(II)(DMSO)₄Cl₂]⁰ was slightly lower. Only cis-PDD and [cis-Ru(II)(DMSO)₄Cl₂]⁰ had any significant activity against L1210 leukemia.

The histological damage caused by the compounds tested was moderate and was virtually absent for [RhacacCOD]⁰, on intestinal mucosa and spleen, when compared with that of cis-PDD. Labeled precursor incorporation into macromolecules of tumor cells showed a selective depression of uridine incorporation for [RhacacCOD]. [cis-Ru(II)(DMSO)₄Cl₂]⁰, however, caused a similar inhibition of incorporation of thymidine, uridine, and leucine at the highest dosage tested, but no such effects were observed at the two lower dosages that were still therapeutically useful.

Our findings indicate that, in the experimental systems used, [RhacacCOD]⁰ and [cis-Ru(II)(DMSO)₄Cl₂]⁰ have a therapeutic efficacy better than or equal to that displayed by cis-PDD, and that they may have a different mode of action.

¹ Supported by Consiglio Nazionale delle Ricerche Contract 75.00585.04.

² Permanent address: Guardia Chirurgica, Ospedali Riuniti, Trieste.

Received 10/21/76. Accepted 3/ 4/77.