Synthesis and antitumor activity of a new cis-diammineplatinum (II) complex containing procaine hydrochloride

Anticancer Res. 1992 Nov-Dec;12(6B):2285-92.

Abstract

This paper refers to some of the chemical and biological properties of a new platinum (II) complex where the aromatic amino group of procaine is involved in the coordination with platinum and whose structure was defined by UV, IR, 1H-NMR, and elemental analysis. This new cationic platinum-triamine complex (DPR) displays excellent solubility (> 50 mg/ml) and stability in water. DPR has significant in vitro cytotoxicity against murine P388 leukemic cell line, human K562 erythroleukemic cell line and human Jurkat T cell line. The in vitro cytotoxic effects of DPR on P388 and Jurkat leukemic cells were comparable to those of cis-diamminedichloroplatinum (II) (DDP), while its activity on K562 cells was significantly better than that of DDP [IC50 = 1.07 +/- 0.36 (SD) microM vs 2.62 +/- 0.23 (SD) microM, P < 0.01]. The in vitro Pt accumulation rate for P388 cells was twice as rapid after DPR than after DDP exposure, while no difference in cellular platinum efflux was observed. The antitumor activity of DPR was tested in vivo against P388 leukemic cells in BDF1 mice and gave a % ILS value (75%) similar to that of the maximum tolerated dose (MTD) of DDP (8 mg/Kg). A comparative study of plasma urea nitrogen (PUN) levels and kidney morphological analysis in tumor-bearing mice receiving the LD50 dose of both drugs (39.3 mg/Kg and 16.5 mg/Kg for DPR and DDP, respectively), showed DPR to be less nephrotoxic than DDP. These results indicate that this new cationic platinum-triamine complex containing primary amine ligand is surprisingly active both in vitro and in vivo. In summary, the good characteristics of DPR in terms of high solubility, encouraging anticancer activity and absence of nephrotoxic effects make DPR a promising new platinum anticancer agent for preclinical development.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Biological Transport
  • Blood Urea Nitrogen
  • Cell Division / drug effects
  • Cell Survival / drug effects
  • Cisplatin / analogs & derivatives*
  • Cisplatin / chemical synthesis
  • Cisplatin / metabolism
  • Cisplatin / therapeutic use*
  • Cisplatin / toxicity
  • Female
  • Humans
  • Kidney / drug effects
  • Kidney / pathology
  • Leukemia P388 / drug therapy*
  • Leukemia P388 / metabolism
  • Leukemia, Erythroblastic, Acute
  • Lymphoma
  • Mice
  • Mice, Inbred Strains
  • Organoplatinum Compounds*
  • Procaine / analogs & derivatives*
  • Procaine / chemical synthesis
  • Procaine / therapeutic use
  • Procaine / toxicity
  • Thymidine / metabolism
  • Tumor Cells, Cultured
  • Tumor Stem Cell Assay

Substances

  • Organoplatinum Compounds
  • cisplatin-procaine complex
  • Procaine
  • Cisplatin
  • Thymidine