title: Synthesis, molecular docking and binding studies of selective serotonin transporter inhibitors.
abstract: With the aim of obtaining compounds possessing high SERT selectivity, in the present work we synthesized and studied the inhibition of serotonin (SERT), dopamine (DAT) and norepinephrine (NET) transporters by docking studies and experimental binding measurements of a series of 4-(aryl)piperidin-3-one O-4-benzyl oxime hydrochlorides (1-10) of both E and Z configuration. E configuration compounds showed high SERT binding affinities (K(i) = 10-98 nM) and high SERT selectivities over both NET and DAT. The molecular docking studies allowed a rationalization of the molecular basis of drug-SERT interactions both of the synthesized compounds and paroxetine and fluoxetine used as reference antidepressant drugs.
authors.affiliation: Dipartimento di Scienze Farmaceutiche, Università di Pisa, Via Bonanno 6, 56126 Pisa, Italy. nencettis@farm.unipi.it
authors.forename: Susanna
authors.initials: S
authors.lastname: Nencetti
authors.forename: Maria R
authors.initials: MR
authors.lastname: Mazzoni
authors.forename: Gabriella
authors.initials: G
authors.lastname: Ortore
authors.forename: Annalina
authors.initials: A
authors.lastname: Lapucci
authors.forename: Janette
authors.initials: J
authors.lastname: Giuntini
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Orlandini
authors.forename: Irene
authors.initials: I
authors.lastname: Banti
authors.forename: Elisa
authors.initials: E
authors.lastname: Nuti
authors.forename: Antonio
authors.initials: A
authors.lastname: Lucacchini
authors.forename: Gino
authors.initials: G
authors.lastname: Giannaccini
authors.forename: Armando
authors.initials: A
authors.lastname: Rossello
mesh_terms: D000818:Animals; D004298:Dopamine / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D018377:Neurotransmitter Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D009638:Norepinephrine / Q000037:antagonists & inhibitors*; D010880:Piperidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D011485:Protein Binding; D011817:Rabbits; D012701:Serotonin / Q000378:metabolism*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism; D017367:Selective Serotonin Reuptake Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D004298:Dopamine; D018377:Neurotransmitter Agents; D009638:Norepinephrine; D010880:Piperidines; D012701:Serotonin; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; C032727:piperidine