Antileukemic and cytogenetic activity by triple administration of three modified steroidal derivatives of nitrogen mustards

Chemotherapy. 2007;53(2):118-26. doi: 10.1159/000099983. Epub 2007 Feb 16.

Abstract

Combination chemotherapy is widely and routinely used for most cancer patients. The main objective of this study is an effort to develop new anticancer drugs and procedures with enhanced antitumor activity and reduced toxicity. This study was designed to determine the antileukemic and cytogenetic activity of five mixtures of three specific steroidal esters of aromatic nitrogen mustards in different proportions. This is the next step of two previous studies where the combination of two such esteric analogues was investigated with promising results. All of the five mixtures used proved active against leukemia P388 and in the induction of sister chromatid exchanges, indicating that the combination of the same class of compounds can be successful, especially when a highly potent agent is combined with another less active but probably mechanistically supplementary one. These results can be used in future experiments in order to further scout the specific role of the steroidal part of these molecules in the antileukemic potency of them.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Androstanes / pharmacology*
  • Animals
  • Antineoplastic Agents / pharmacology*
  • Azasteroids / pharmacology*
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Drug Synergism
  • Female
  • Humans
  • Lethal Dose 50
  • Leukemia P388 / drug therapy*
  • Lymphocytes / drug effects
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred DBA
  • Nitrogen Mustard Compounds / pharmacology*
  • Sister Chromatid Exchange
  • Xenograft Model Antitumor Assays

Substances

  • Androstanes
  • Antineoplastic Agents
  • Azasteroids
  • Nitrogen Mustard Compounds
  • 3-hydroxy-N-methyl-17-aza-D-homoandrostan-17-one-4-N,N-bis(2-chloroethyl)aminophenylacetate