Design, synthesis, and evaluation of estradiol-linked genotoxicants as anti-cancer agents

Bioorg Med Chem Lett. 2004 Jul 16;14(14):3829-33. doi: 10.1016/j.bmcl.2004.04.064.

Abstract

A series of bifunctional compounds was prepared consisting of 17beta estradiol linked to a DNA damaging N,N-bis-(2-chloroethyl)aniline. The objective of our studies was to determine the characteristics of the linker that permitted both reaction with DNA and binding of the resultant covalent adducts to the estrogen receptor. Linker characteristics were pivotal determinants underlying the ability of the compounds to kill selectively breast cancer cells that express the estrogen receptor.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aniline Compounds / chemistry
  • Aniline Compounds / pharmacology
  • Aniline Compounds / therapeutic use*
  • Aniline Mustard
  • Antineoplastic Agents, Alkylating / chemical synthesis*
  • Antineoplastic Agents, Alkylating / pharmacology
  • Antineoplastic Agents, Alkylating / therapeutic use
  • Binding Sites
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism
  • Cell Survival / drug effects*
  • DNA Adducts / metabolism
  • Dose-Response Relationship, Drug
  • Drug Design
  • Estradiol / chemistry
  • Estradiol / pharmacology
  • Estradiol / therapeutic use*
  • Evaluation Studies as Topic
  • Female
  • Humans
  • Receptors, Estrogen / metabolism
  • Tumor Cells, Cultured

Substances

  • Aniline Compounds
  • Antineoplastic Agents, Alkylating
  • DNA Adducts
  • Receptors, Estrogen
  • Estradiol
  • Aniline Mustard