Pharmacological Effects of the Ruthenium Complex NAMI-A Given Orally to CBA Mice With MCa Mammary Carcinoma

NAMI-A, imidazolium trans-imidazoledimethylsulfoxidetetrachlororuthenate, is a ruthenium based compounds capable of inhibiting the growth of lung metastases of solid tumours in a number of experimental conditions.The aim of this study was to investigate the potential use of NAMI-A by the oral route to treat lung metastases of MCa mammary carcinoma in the CBA mouse. treatment of mice, carrying intramuscular tumours in advanced stage of growth, for 11 consecutive days caused a significant reduction of the weight of lung metastases over the range of doses from 150 to 600 mg/kg/day. No sign of toxicity was observed at the histological analysis in the gut epithelium or in the kidney parenchyma, and NAMI-A concentration in the kidney was more than 10-fold lower than after intraperitoneal treatments. NAMI-A is thus active against metastases also by the oral route, suggesting the use of this way to treat tumour bearing hosts for long periods

Reduction of Lung Metastases by Na[trans-RuCl4(DMSO)Im] is not Coupled With the Induction of Chemical Xenogenization

The effects of the treatment of tumor cells of MCa mammary carcinoma and TLX5 lymphoma with the ruthenium complex Na[trans-RuCl4 (DMSO)lm] for several transplant generations were studied on tumor growth and metastases formation. On TLX5 lymphoma cells, treatment was performed in vitro prior to in vivo inoculation of tumor cells in intact or immunesuppressed mice. Either considering tumor take and growth or its capacity to invade the brain of the inoculated hosts, Na[trans-RuCl4(DMSO)lm] did not induce any significant modification. Conversely, in mice with MCa mammary carcinoma, the in vivo treatment of tumor cells in immunesuppressed hosts caused a progressive increase of DNA activity and, starting from the 4th transplant generation, a significantly increased susceptibility of lung metastasis formation to a further treatment in intact mice. These data seem to suggest that Na[trans-RuCl4(DMSO)Im] does not induce chemical xenogenization of tumor cells nor its repeated treatment induces resistance in tumor cells. Conversely, it appears that Na[trans-RuCl4(DMSO)lm] may select a tumor cell population which maintains its capacity to metastasise to the lung but with enhanced sensitivity to the antimetastatic properties of this compound

Bis(2,9-dimethyl-1,10-phenanthroline-κ2 N,N′)(10,11,12,13-tetra­hydro­dipyrido[3,2-a:2′,3′-c]phenazine-κ2 N 4,N 5)ruthenium(II) bis­(perchlorate) dihydrate

The title compound, [Ru(C14H12N2)2(C18H14N4)](ClO4)2·2H2O, consists of an RuII complex cation, two perchlorate anions and two uncoordinated water mol­ecules. The RuII ion is chelated by a 10,11,12,13-tetra­hydro­dipyrido[3,2-a:2′,3′-c]phenazine ligand and two 2,9-dimethyl-1,10-phenanthroline ligands in a distorted octa­hedral geometry. The two uncoord­inated water mol­ecules are disordered over five positions, with an occupancy factor of about 0.4 for each site. A supra­molecular structure is formed by weak π–π inter­actions between neighbouring mol­ecules, with centroid–centroid distances of 3.618 (2) and 3.749 (2) Å

Inhibition of endothelial cell functions and of angiogenesis by the metastasis inhibitor NAMI-A

NAMI-A is a ruthenium-based compound with selective anti-metastasis activity in experimental models of solid tumours. We studied whether this activity was dependent on anti-angiogenic ability of NAMI-A. We thus investigated its in vitro effects on endothelial cell functions necessary for angiogenesis to develop, as well as its in vivo effects in the chick embryo chorioallantoic membrane model. Endothelial cell proliferation, chemotaxis, and secretion of the matrix-degrading enzyme metalloproteinase-2 were inhibited by NAMI-A in a dose-dependent manner, and without morphologic signs of cell apoptosis or necrosis. Lastly, NAMI-A displayed a dose-dependent in vivo anti-angiogenic activity in the chorioallantoic membrane model. These data suggest that the anti-angiogenic activity of NAMI-A can contribute to its anti-metastatic efficacy in mice bearing malignant solid tumours