SYNTHESIS AND CHARACTERIZATION OF A NEW BILE-ACID AND PLATINUM(II) COMPLEX WITH CYTOSTATIC ACTIVITY

With a vie iv to using bile acids as shuttles for delivering platinum- related cytostatic drugs to the liver, a cholylglycine (CG)-derivative of platinum(II) has been synthesized. The complex, named Bamet-H2, wa s characterized by elemental analysis, FT-IR, NMR, FAB-MS, and UV spec troscopy. The results indicate the following composition: C52H84N2O12C lNa Pt(II). Conductivity data suggest that the complex behaves as a so dium salt (1:1) of a complex of Pt(II) bound to one Cl-, one bidentate CG moiety, and another monodentate CG moiety, i.e., Na[Pt(CG-O,N) (CG -O)Cl]. The compound is highly soluble (up to 10 mM) in water, ethanol , methanol, DMF, and DMSO. Bamet-H2 was stable in solution (either wat er or 150 mM NaCl solution), as measured by HPLC, up to 24 h. At this time, more than 90% of the platinum present in water or saline solutio ns was found to be Bamet-H2. Cytostatic activity against L1210 murine leukemia cells was found. This characteristic was stronger against rat hepatocytes in primary culture. Isolated in situ rat livers were perf used for 40 min with a recirculating medium containing 1 mu M Barnet-H 2, CG, or cisplatin. Uptake and excretion into bile were much greater for Bamet-H2 than for cisplatin, but less than for CG. Liver content w as higher for Bamet-H2 than for cisplatin or CG. The results point to the potential usefulness of Bamet-H2 in the antitumoral therapy of neo plasias derived from liver parenchymal cells.