The antitumor activity of the organometallic ruthenium(II)-arene complexes, RuCl2(è6-arene)-
(PTA), (arene ) p-cymene, toluene, benzene, benzo-15-crown-5, 1-ethylbenzene-2,3-dimethylimidazolium
tetrafluoroborate, ethyl benzoate, hexamethylbenzene; PTA ) 1,3,5-triaza-7-
phosphaadamantane), abbreviated RAPTA, has been evaluated. In vitro biological experiments
demonstrate that these compounds are active toward the TS/A mouse adenocarcinoma cancer
cell line whereas cytotoxicity on the HBL-100 human mammary (nontumor) cell line was not
observed at concentrations up to 0.3 mM, which indicates selectivity of these ruthenium(II)-
arene complexes to cancer cells. Analogues of the RAPTA compounds, in which the PTA ligand
is methylated, have also been prepared, and these prove to be cytotoxic toward both cell lines.
RAPTA-C and the benzene analogue RAPTA-B were selected for in vivo experiments to evaluate
their anticancer and antimetastatic activity. The results show that these complexes can reduce
the growth of lung metastases in CBA mice bearing the MCa mammary carcinoma in the
absence of a corresponding action at the site of primary tumor growth. Pharmacokinetic studies
of RAPTA-C indicate that ruthenium is rapidly lost from the organs and the bloodstream.
