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.

Synthesis, molecular docking and binding studies of selective serotonin transporter inhibitors

NENCETTI, SUSANNA;MAZZONI, MARIA ROSA;ORTORE, GABRIELLA MARIA PIA;LAPUCCI, ANNALINA;ORLANDINI, ELISABETTA;NUTI, ELISA;LUCACCHINI, ANTONIO;GIANNACCINI, GINO;ROSSELLO, ARMANDO
2011-01-01

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.
2011
Nencetti, Susanna; Mazzoni, MARIA ROSA; Ortore, GABRIELLA MARIA PIA; Lapucci, Annalina; Giuntini, Janette; Orlandini, Elisabetta; Banti, Irene; Nuti, Elisa; Lucacchini, Antonio; Giannaccini, Gino; Rossello, Armando
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11568/189250
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