Anti-cancer activity of di- and tri-organotin(iv) compounds with D-(+)-Galacturonic acid on human tumor cells.

We have compared the anti-proliferative activity in vitro, of R2SnGala (1-3) [R=Me, Bu, Ph] and novel R3SnGala (4, 5) [R= Me, Bu] with D-(+)-Galacturonic acid [HGala; Galaq- , q= (2-) and (1-) for R2SnGala and R3SnGala, respectively] compounds, toward human tumor cell lines of intestinal carcinoma (HCT-116) and breast adenocarcinoma (MCF-7). The new synthesized 4 and 5 compounds were characterized, in solution, by 1H,13C and 119Sn NMR experiments, which showed that HGala acts as monoanionic moiety as well as enlightened the dynamic behavior of the compounds, due to inter-conversions involving the anomeric carbon atom of the ligand. Cell viability, apoptosis induction and cell cycle distribution were analyzed by MTT and flow cytometry, respectively. Citotoxicity of compounds, in the micro-submicromolar range, changed in the order of the organotin(IV) moieties, according to 5>3>2, while 1 and 4, containing MenSn(IV)(n=2,3) moieties, were ineffective. Compound 5 showed peculiar cytotoxic effects. It did not cause time dependent inhibition of cell growth nor accumulate into the cells. Cell death induced by the active 2, 3, and 5, was considered to be apoptotic by measuring the exposure of phosphatidylserine to the outer membrane and the loss of mitochondrial potential. All the cytotoxic compounds induced an accumulation of cells in the subG0/G1phase, while only 2 and 3 perturbed the cell cycle confining viable cells in G0/G1phase. Finally, none of the compound investigated affected the viability of normal intestinal cells, indicating selectivity towards tumor cells.