title: Novel potent and selective σ ligands: evaluation of their agonist and antagonist properties.
abstract: Novel enantiomers and diastereoisomers structurally related to σ ligand (+)-MR200 were synthesized to improve σ(1)/σ(2) subtype selectivity. The selective σ(1) ligand (-)-8 showed an antagonist profile determined by phenytoin differential modulation of binding affinity in vitro, confirmed in vivo by an increase of κ opioid analgesia. The σ(2) ligand (-)-9 displayed agonist properties in an in vitro isolated organ bath assay and antiproliferative effects on LNCaP and PC3 prostate cancer cell lines.
authors.affiliation: Department of Drug Sciences, Medicinal Chemistry Section, University of Catania, Viale A. Doria 6, 95125 Catania, Italy. marrazzo@unict.it
authors.forename: Agostino
authors.initials: A
authors.lastname: Marrazzo
authors.forename: Enrique J
authors.initials: EJ
authors.lastname: Cobos
authors.forename: Carmela
authors.initials: C
authors.lastname: Parenti
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Aricò
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Marrazzo
authors.forename: Simone
authors.initials: S
authors.lastname: Ronsisvalle
authors.forename: Lorella
authors.initials: L
authors.lastname: Pasquinucci
authors.forename: Orazio
authors.initials: O
authors.lastname: Prezzavento
authors.forename: Nicola A
authors.initials: NA
authors.lastname: Colabufo
authors.forename: Marialessandra
authors.initials: M
authors.lastname: Contino
authors.forename: Luis G
authors.initials: LG
authors.lastname: González
authors.forename: Giovanna M
authors.initials: GM
authors.lastname: Scoto
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Ronsisvalle
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D003521:Cyclopropanes / Q000819:agonists* / Q000037:antagonists & inhibitors* / Q000138:chemical synthesis*; D015195:Drug Design; D006801:Humans; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008956:Models, Chemical; D009119:Muscle Contraction / Q000187:drug effects; D010880:Piperidines / Q000819:agonists* / Q000037:antagonists & inhibitors* / Q000138:chemical synthesis*; D011485:Protein Binding; D017465:Receptors, Opioid, delta / Q000187:drug effects*; D013997:Time Factors
chemical_list: C479880:(+)-methyl 2-((4-(4-chlorophenyl)-4-hydroxypiperidin-1-yl)methyl)-1-phenylcyclopropanecarboxylate; D003521:Cyclopropanes; D010880:Piperidines; D017465:Receptors, Opioid, delta