Cytotoxicity of enantiomers of gossypol Schiff's bases and optical stability of gossypolone

Eur J Med Chem. 2004 Jul;39(7):619-24. doi: 10.1016/j.ejmech.2004.04.001.

Abstract

Optical Schiff's bases of gossypol were prepared with chiral gossypol and ethylamine. As has been similarly observed among the gossypol enantiomers, the (-)-gossypol ethylimine was more active than either the (+)-gossypol ethylimine or the racemic gossypol ethylimine against KB and MCF7 cells. Gossypolone was also observed to be more toxic than gossypol against both cell lines. All of the gossypol products tested showed comparable toxicity toward MCF7/ADR (adriblastine-resistant) cells. Attempts at producing chiral gossypolone from chiral gossypol failed because of rapid racemization. In addition, the Schiff's base derivatives of gossypolone formed with R-(+)-2-amino-3-phenyl-1-propanol could only be separated at reduced temperature, indicating that gossypolone Schiff's bases are less optical stable than gossypol Schiff's bases.

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Breast Neoplasms / drug therapy*
  • Cell Survival / drug effects
  • Chromatography, High Pressure Liquid
  • Doxorubicin / adverse effects
  • Ethylamines / chemistry
  • Gossypol / analogs & derivatives*
  • Gossypol / chemistry*
  • Gossypol / pharmacology*
  • Humans
  • KB Cells / drug effects
  • Mass Spectrometry
  • Schiff Bases / chemical synthesis
  • Schiff Bases / chemistry
  • Schiff Bases / pharmacology*
  • Stereoisomerism
  • Structure-Activity Relationship
  • Temperature
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • Ethylamines
  • Schiff Bases
  • gossypolone
  • Doxorubicin
  • Gossypol
  • ethylamine