Potential new antitumor agents from an innovative combination of demethylcantharidin, a modified traditional Chinese medicine, with a platinum moiety

J Med Chem. 2001 Jun 21;44(13):2065-8. doi: 10.1021/jm000476t.

Abstract

A combination of demethylcantharidin, a modified component of a traditional Chinese medicine (TCM), with a platinum moiety has produced a series of TCM-based platinum compounds [Pt(C(8)H(8)O(5))(NH(2)R)(2)] 1-5, which demonstrate selective cytotoxicity toward SK-Hep-1 (human liver) cell line, and circumvention of cross-resistance. The inclusion of demethylcantharidin rendered the compounds highly active as protein phosphatase (PP2A) inhibitors. The new TCM-Pt compounds may possess a novel dual mechanism of antitumor action: inhibition of PP2A and platination of DNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / chemistry*
  • Antineoplastic Agents, Phytogenic / therapeutic use
  • Bridged Bicyclo Compounds, Heterocyclic / chemical synthesis*
  • Bridged Bicyclo Compounds, Heterocyclic / pharmacology*
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Cell Division / drug effects
  • DNA, Neoplasm / drug effects
  • Enzyme Inhibitors / pharmacology
  • Humans
  • Leukemia L1210 / drug therapy
  • Liver Neoplasms, Experimental / drug therapy
  • Liver Neoplasms, Experimental / pathology
  • Lung Neoplasms / drug therapy
  • Medicine, Chinese Traditional
  • Mice
  • Mice, Inbred ICR
  • Mice, Nude
  • Neoplasm Transplantation
  • Organoplatinum Compounds / chemistry*
  • Organoplatinum Compounds / therapeutic use
  • Phosphoprotein Phosphatases / antagonists & inhibitors
  • Phytotherapy
  • Plants, Medicinal / chemistry
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents, Phytogenic
  • Bridged Bicyclo Compounds, Heterocyclic
  • DNA, Neoplasm
  • Enzyme Inhibitors
  • Organoplatinum Compounds
  • norcantharidin
  • Phosphoprotein Phosphatases