Synthesis and antitumor activity of 1,2-diaminocyclohexane platinum(IV) complexes

J Inorg Biochem. 1994 Apr;54(1):39-47. doi: 10.1016/0162-0134(94)85122-0.

Abstract

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

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / therapeutic use
  • Antineoplastic Agents / toxicity
  • Cell Survival / drug effects
  • Cisplatin / toxicity
  • Drug Resistance
  • Indicators and Reagents
  • Leukemia L1210 / drug therapy
  • Lymphoma, Large B-Cell, Diffuse / drug therapy
  • Magnetic Resonance Spectroscopy / methods
  • Melanoma, Experimental / drug therapy
  • Mice
  • Mice, Inbred Strains
  • Organoplatinum Compounds / chemical synthesis*
  • Organoplatinum Compounds / therapeutic use
  • Organoplatinum Compounds / toxicity
  • Structure-Activity Relationship
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • Indicators and Reagents
  • Organoplatinum Compounds
  • Cisplatin