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.
Suzanne M Cloonan  1 ,  John J Keating ,  Stephen G Butler ,  Andrew J S Knox ,  Anne M Jørgensen ,  Günther H Peters ,  Dilip Rai ,  Desmond Corrigan ,  David G Lloyd ,  D Clive Williams ,  Mary J Meegan
Affiliations
  • 1. School of Biochemistry and Immunology, Trinity College Dublin, Ireland.
PMID: 19717215 DOI: 10.1016/j.ejmech.2009.07.027
Abstract

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.