SYNTHESIS AND CYTOTOXIC ACTIVITY OF DEXTRAN CARRYING HLORO(CYCLOHEXANE-TRANS-L-1,2-DIAMINE)PLATINUM(II) COMPLEX

hloro(cyclohexane-trans-l-1,2-diamine)platinum(II) (Dach-Pt(chlorato)) , is a platinum complex which is expected to exhibit higher antitumor activity than, and show no cross resistance with. cisplatin. However, its strong side-effects and low water-solubility have also been cited. We report that polymer/antitumor drug conjugates shows reduced side-e ffects and high antitumor activity. In order to provide a macromolecul ar prodrug of Dach-Pt having reduced side-effects and high water-solub ility, we synthesized polymer conjugates of Dach-Pt and dextran deriva tives having carboxylic acid groups, oxidized-dextran (OX-Dex)/Dach-Pt conjugate, and carboxymethyl-dextran(CM-Dex)/Dach-Pt conjugate. The c ytotoxic activities of the conjugates were investigated against p388D( 1) lymphocytic leukemia cells in vitro. The OX-Dex/Dach-Pt conjugate s howed almost the same level of cytotoxic activity as free Dach-Pt(chlo rato). Although the cytotoxic activity of free Dach-Pt(chlorato) was d ecreased by incubation in medium with serum, the OX-Dex/Dach-Pt conjug ate kept its cytotoxic activity in higher level after 24 h incubation in medium with serum. These results suggested that the stability of Da ch-Pt molecule in the medium was increased and cytotoxic activity of D ach-Pt was not decreased by Axing to OX-Dex.