Synthesis of 4,4'-Diaminotriphenylmethanes with Potential Selective Estrogen Receptor Modulator (SERM)-like Activity

ChemMedChem. 2015 Aug;10(8):1403-12. doi: 10.1002/cmdc.201500148. Epub 2015 Jun 15.

Abstract

In this study, a series of new 4,4'-diaminotriphenylmethanes was efficiently synthesized from aromatic aldehydes and 2,5-dimethoxybenzenamine under microwave irradiation in the presence of Sc(OTf)3 as a catalyst. Antiproliferative activity was assessed by using the MCF-7 estrogen receptor (ER)-positive breast cancer cell line, and antagonist/agonist transcriptional activities were determined. Docking studies and competition studies of triphenylmethanes and radiolabeled estradiol determined that these compounds do not bind the ER, indicating that triphenylmethane-induced changes in proliferative and transcriptional activities differ from conventional mechanisms of action triggered by other selective ER modulators.

Keywords: estrogen receptors; molecular docking; selective modulation; triarylmethanes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Cell Proliferation / drug effects
  • Female
  • Humans
  • MCF-7 Cells
  • Methane / chemical synthesis
  • Methane / chemistry*
  • Methane / toxicity
  • Molecular Docking Simulation
  • Protein Binding
  • Protein Structure, Tertiary
  • Receptors, Estrogen / chemistry
  • Receptors, Estrogen / genetics
  • Receptors, Estrogen / metabolism*
  • Selective Estrogen Receptor Modulators / chemical synthesis*
  • Selective Estrogen Receptor Modulators / chemistry
  • Selective Estrogen Receptor Modulators / toxicity
  • Transcriptional Activation / drug effects

Substances

  • Receptors, Estrogen
  • Selective Estrogen Receptor Modulators
  • Methane