Synthesis of a new nor-aza-steroidal ester of p-N,N-bis-(2-chloroethyl)aminophenylbutyric acid and in vitro study of its mutagenicity and clastogenicity

Oncology. 1986;43(6):390-4. doi: 10.1159/000226408.

Abstract

A new nor-aza-steroidal ester of chlorambucil has been synthesized. The study of the mitotic index in CHO and HeLa cells treated with this compound showed that it may be a cytostatic drug. It was also found that treatment of CHO cells with a dose as low as 5 micrograms/ml induces a large number of sister chromatid exchanges. A great number of abnormal metaphases has been observed when CHO cells were treated with the compound at a dose of 25 micrograms/ml. When the compound was tested in the Ames/Salmonella microsome assay, it was found to be mutagenic in strains TA100 and TA1535, both with and without metabolic activation.

MeSH terms

  • Animals
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / toxicity*
  • Azasteroids / chemical synthesis
  • Azasteroids / toxicity*
  • Carcinogens
  • Cells, Cultured
  • Chlorambucil / analogs & derivatives*
  • Chlorambucil / chemical synthesis
  • Chlorambucil / toxicity
  • Metaphase / drug effects
  • Mutagens*
  • Rats
  • Steroids, Heterocyclic / toxicity*

Substances

  • Antineoplastic Agents
  • Azasteroids
  • Carcinogens
  • Mutagens
  • Steroids, Heterocyclic
  • 17-hydroxy-4-aza-A-nor-5-androsten-3-one (4-N,N-bis(2-chloroethylamino)phenyl)butyrate
  • Chlorambucil