Synthesis and serotonin transporter activity of sulphur-substituted alpha-alkyl phenethylamines as a new class of anticancer agents

Eur J Med Chem. 2009 Dec;44(12):4862-88. doi: 10.1016/j.ejmech.2009.07.027. Epub 2009 Aug 6.


The discovery that some serotonin reuptake transporter (SERT) ligands have the potential to act as pro-apoptotic agents in the treatment of cancer adds greatly to their diverse pharmacological application. 4-Methylthioamphetamine (MTA) is a selective ligand for SERT over other monoamine transporters. In this study, a novel library of structurally diverse 4-MTA analogues were synthesised with or without N-alkyl and/or C-alpha methyl or ethyl groups so that their potential SERT-dependent antiproliferative activity could be assessed. Many of the compounds displayed SERT-binding activity as well as cytotoxic activity. While there was no direct correlation between these two effects, a number of derivatives displayed anti-tumour effects in lymphoma, leukaemia and breast cancer cell lines, showing further potential to be developed as possible chemotherapeutic agents.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amphetamines / chemical synthesis
  • Amphetamines / chemistry
  • Amphetamines / pharmacology
  • Animals
  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Humans
  • Inhibitory Concentration 50
  • Models, Molecular
  • Molecular Structure
  • Phenethylamines / chemical synthesis*
  • Phenethylamines / chemistry
  • Phenethylamines / pharmacology*
  • Serotonin Plasma Membrane Transport Proteins / drug effects
  • Serotonin Plasma Membrane Transport Proteins / metabolism*
  • Structure-Activity Relationship
  • Sulfur* / chemistry


  • Amphetamines
  • Antineoplastic Agents
  • Phenethylamines
  • Serotonin Plasma Membrane Transport Proteins
  • 4-methylthioamphetamine
  • Sulfur