Structural characterization, kinetic studies, and in vitro biological activity of new cis-diamminebis-cholylglycinate (O,O ') Pt(II) and cis-diamminebis-ursodeoxycholate(O,O ') Pt(II) complexes

The complexes cis-diamminebis-cholylglycinate (O,O') [Pt(II) C52H90N4O12Pt, for convenience referred to as Bamet-R1] and cis-diamminebis-ursodeoxychol ate (O,O') Pt(II) (C48H84N2O8Pt, Bamet-UD2) were prepared. The structural i ntegrity of the compounds was confirmed by elemental analysis, FT-IR, NMR, FAR-MS, and UV spectroscopies. The kinetic study of both compounds was acco mplished by combining the conductivity measurement and those of the analysi s of the electronic spectra in aqueous solution for NaCl concentrations of 4 mM (similar to cytoplasmatic concentration), 150 mM (similar to plasmatic concentration), and 500 mM. In water, the compound Bamet-R1 showed a half- life, t(1/2), of 3.0 h. This compound forms the chelate species through los s of a ligand, and the other one acts as a bidentate ligand. Ring opening i n the presence of chloride ion was produced with a k(Cl)- of 0.25 M-1 h(-1) The half-life of Bamet-UD2 in aqueous solution was 3.2 h. However, since t his species is not able to chelate and has a lower degree of solubility in the presence of chloride ion, its kinetic behavior was very different from that of the other compound. We consider this to be of great interest with r egards to its cytostatic activity. All kinetic measurements were performed under pseudo-first-order conditions, and a pseudo-first-order behavior was found. The antitumoral effect of Bamet-UD2 on several cell lines derived fr om rat hepatoma, human hepatoma, mouse leukemia, and human colon carcinoma was found to be, in general, similar to that of cisplatin, but higher than that observed for Bamet-R1.