title: Synthesis and serotonin transporter activity of sulphur-substituted alpha-alkyl phenethylamines as a new class of anticancer agents.
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.
authors.affiliation: School of Biochemistry and Immunology, Trinity College Dublin, Ireland.
authors.forename: Suzanne M
authors.initials: SM
authors.lastname: Cloonan
authors.forename: John J
authors.initials: JJ
authors.lastname: Keating
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Butler
authors.forename: Andrew J S
authors.initials: AJ
authors.lastname: Knox
authors.forename: Anne M
authors.initials: AM
authors.lastname: Jørgensen
authors.forename: Günther H
authors.initials: GH
authors.lastname: Peters
authors.forename: Dilip
authors.initials: D
authors.lastname: Rai
authors.forename: Desmond
authors.initials: D
authors.lastname: Corrigan
authors.forename: David G
authors.initials: DG
authors.lastname: Lloyd
authors.forename: D Clive
authors.initials: DC
authors.lastname: Williams
authors.forename: Mary J
authors.initials: MJ
authors.lastname: Meegan
mesh_terms: D000662:Amphetamines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D015394:Molecular Structure; D010627:Phenethylamines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000187:drug effects / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013455:Sulfur / Q000737:chemistry
chemical_list: D000662:Amphetamines; D000970:Antineoplastic Agents; D010627:Phenethylamines; D050486:Serotonin Plasma Membrane Transport Proteins; C078956:4-methylthioamphetamine; D013455:Sulfur