Cytotoxicity of 2,2':6',2' '-terpyridineplatinum(II) complexes against human ovarian carcinoma

J Med Chem. 1999 Aug 12;42(16):3167-74. doi: 10.1021/jm991053y.

Abstract

2,2':6',2''-Terpyridineplatinum(II) complexes are shown to possess cytotoxicity against a number of human ovarian tumor cell lines. Many of the complexes show similar activity against cisplatin- and doxorubicin-resistant cell lines as the parental cells suggesting that there is little or no cross-resistance with cisplatin or doxorubicin. The cytotoxicity of bis[2,2':6',2''-terpyridineplatinum(II)] complexes is strongly dependent on the nature of the linker. Bis[2,2':6',2''-terpyridineplatinum(II)] complexes with a flexible linker at the 4'-position show poor cytotoxicity; by contrast bis[2,2':6',2''- terpyridineplatinum(II)] complexes with rigid and short linkers at platinum(II) are strikingly effective. Several of the compounds show greater cytotoxicity against human ovarian cell lines than carboplatin, the therapeutic agent currently advocated for the treatment of human ovarian cancers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Drug Resistance, Multiple
  • Drug Resistance, Neoplasm
  • Drug Screening Assays, Antitumor
  • Female
  • Humans
  • Inhibitory Concentration 50
  • Organoplatinum Compounds / chemical synthesis*
  • Organoplatinum Compounds / chemistry
  • Organoplatinum Compounds / pharmacology
  • Ovarian Neoplasms / pathology
  • Pyridines / chemical synthesis*
  • Pyridines / chemistry
  • Pyridines / pharmacology
  • Structure-Activity Relationship
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • Organoplatinum Compounds
  • Pyridines