Synthesis, mutagenicity, binding to pBR 322 DNA and antitumour activity of platinum(II) complexes with ethambutol

Anticancer Res. 1991 Jan-Feb;11(1):281-7.

Abstract

Platinum complexes with N,N'-bis(1-hydroxybut-2-yl)ethylenediamine, [PtCl2(ethambutol)] were prepared and the biological activity of three isomers [with (-), (+) and (+/-) ethambutol, respectively] investigated. All species interact with the Bam HI and Ava I recognition sequences showing a binding preference for GC rich sequences of DNA. The complex which showed the greatest interaction with adjacent guanines, [PtCl2[+/-)ethambutol)] was also found to be the most mutagenic of the three. On the other hand, only [PtCl2[+)ethambutol)] had a considerable antitumour activity against both P388 leukaemia and Lewis lung carcinoma, and this was not correlated either with restriction enzyme blocking activity or with mutagenicity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use*
  • Binding Sites
  • Cisplatin / pharmacology*
  • Ethambutol / analogs & derivatives*
  • Ethambutol / chemical synthesis
  • Ethambutol / pharmacology*
  • Ethambutol / therapeutic use
  • Leukemia P388 / drug therapy*
  • Lung Neoplasms / drug therapy*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred DBA
  • Mice, Inbred Strains
  • Molecular Structure
  • Mutagenicity Tests
  • Mutagens / pharmacology*
  • Organoplatinum Compounds / chemical synthesis
  • Organoplatinum Compounds / pharmacology*
  • Organoplatinum Compounds / therapeutic use
  • Plasmids*
  • Restriction Mapping
  • Salmonella typhimurium / drug effects

Substances

  • Antineoplastic Agents
  • Mutagens
  • Organoplatinum Compounds
  • platinum-ethambutol
  • Ethambutol
  • Cisplatin