SYNTHESIS AND ANTITUMOR-ACTIVITY OF 1,2-DIAMINOCYCLOHEXANE PLATINUM(IV) COMPLEXES

The synthesis, characterization, and antitumor activity of a series of platinum(IV) complexes of the type DACH-Pt-IV(X)(2)Y (where DACH = tr ans-dl, or trans-l-1,2-diaminocyclohexane, X = OH or Cl, and Y = oxala to, malonato, methylmalonato, tartronato, ketomalonato, 1,1-cyclopropa nedicarboxylato, or 1,1-cyclobutanedicarboxylato, are described. These complexes have been characterized by elemental analysis, HPLC, and in frared and Pt-195 NMR spectroscopic techniques. The complexes had good in vitro cytotoxic activity (IC50 = 0.14-7.6 mu g/ml) and were highly active in vivo against leukemia L1210 cells (%T/C = 152- > 600, cispl atin = 218). In addition, excellent in vivo antitumor activities again st B16 melanoma (%T/C = 309), M5076 reticulosarcoma (100% cures) and c isplatin-resistant L1210/DDP (%T/C = 217) cell lines were also exhibit ed by an analog selected for further evaluation.