Abstract
Imidazolium trans-imidazoledimethylsulphoxidetetrachlororuthenate ImH[trans-RuCl4 (DMSO)Im] (NAMI-A), a ruthenium compound that replaces Na+ with ImH+ in the molecule of Na[trans-RuCl4 (DMSO)Im] (NAMI), was studied for the anti-metastasis effects in models of solid metastasizing tumours of the mouse. NAMI-A, given i.p. at 35 mg/kg/day for six consecutive days, a dose equimolar to that of NAMI, to mice bear-ing Lewis lung carcinoma and MCa mammary carcinoma, markedly reduces lung metastasis weight by 80-90%, with an effect equal or even superior to that of NAMI, depending on the experimental system adopted. Correspondingly, NAMI-A increases the content of connective tissue in the tumour matrix, around blood vessels, and in the tumour capsule, augments the percentage of tumour cells in G 2 /M phase and reduces the amount of CD45 cells infiltrating the tumour parenchyma. The effects of the same doses on spleen lymphocytes correspond to an increase of CD8 subset without any change of t he distribution of cells in G 0 /G 1 , S and G 2 /M phases. The study shows that NAMI-A behaves similarly to NAMI on the several parameters examined in com-parison experiments and therefore we suggest to credit NAMI-A with all the biological actions already described for NAMI during the last 3 years. The replacement of Na+ with ImH+ therefore, besides the better chemical stability of the molecule, confers to [trans-RuCl4 (DMSO)Im] - a closer similarity with a true drug to be used in humans, and suggests this molecule for future studies of preclinical toxicology and phase I and II clinical trials.© Rapid Science Ltd.
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Sava, G., Capozzi, I., Clerici, K. et al. Pharmacological control of lung metastases of solid tumours by a novel ruthenium complex. Clin Exp Metastasis 16, 371–379 (1998). https://doi.org/10.1023/A:1006521715400
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DOI: https://doi.org/10.1023/A:1006521715400