Illuminating the norepinephrine transporter: fluorescent probes based on nisoxetine and talopram.

Autor: Camacho-Hernandez GA; Medicinal Chemistry Section, Molecular Targets and Medications Discovery Branch, National Institutes of Drug Abuse - Intramural Research Program Baltimore MD 21224 USA anewman@intra.nida.nih.gov., Casiraghi A; Medicinal Chemistry Section, Molecular Targets and Medications Discovery Branch, National Institutes of Drug Abuse - Intramural Research Program Baltimore MD 21224 USA anewman@intra.nida.nih.gov.; Department of Pharmaceutical Sciences, University of Milan Via Mangiagalli 25 20133 Milan Italy., Rudin D; Institute of Pharmacology, Center for Physiology and Pharmacology, Medical University of Vienna Waehringer Strasse 13a 1090 Vienna Austria., Luethi D; Institute of Pharmacology, Center for Physiology and Pharmacology, Medical University of Vienna Waehringer Strasse 13a 1090 Vienna Austria.; Institute of Applied Physics TU Wien, Lehárgasse 6 1060 Vienna Austria., Ku TC; Medicinal Chemistry Section, Molecular Targets and Medications Discovery Branch, National Institutes of Drug Abuse - Intramural Research Program Baltimore MD 21224 USA anewman@intra.nida.nih.gov., Guthrie DA; Medicinal Chemistry Section, Molecular Targets and Medications Discovery Branch, National Institutes of Drug Abuse - Intramural Research Program Baltimore MD 21224 USA anewman@intra.nida.nih.gov., Straniero V; Department of Pharmaceutical Sciences, University of Milan Via Mangiagalli 25 20133 Milan Italy., Valoti E; Department of Pharmaceutical Sciences, University of Milan Via Mangiagalli 25 20133 Milan Italy., Schütz GJ; Institute of Applied Physics TU Wien, Lehárgasse 6 1060 Vienna Austria., Sitte HH; Institute of Pharmacology, Center for Physiology and Pharmacology, Medical University of Vienna Waehringer Strasse 13a 1090 Vienna Austria., Newman AH; Medicinal Chemistry Section, Molecular Targets and Medications Discovery Branch, National Institutes of Drug Abuse - Intramural Research Program Baltimore MD 21224 USA anewman@intra.nida.nih.gov.
Jazyk: angličtina
Zdroj: RSC medicinal chemistry [RSC Med Chem] 2021 Jun 09; Vol. 12 (7), pp. 1174-1186. Date of Electronic Publication: 2021 Jun 09 (Print Publication: 2021).
DOI: 10.1039/d1md00072a
Abstrakt: The utilization of fluorescent ligands to study the monoamine transporters (MATs) has increased our knowledge of their function and distribution in live cell systems. In this study, we extend SAR for nisoxetine and talopram as parent compounds, to identify high affinity rhodamine-labeled fluorescent probes for the norepinephrine transporter (NET). Nisoxetine-based fluorescent probe 6 demonstrated high binding affinity ( K i = 43 nM) for NET and an overall selectivity compared to the other transporters for dopamine (DAT; K i = 1540 nM) and serotonin (SERT; K i = 785 nM) in competitive radioligand binding assays. Using confocal microscopy, compound 6 was shown to stain both NET and SERT, but not DAT, at low nanomolar concentrations, in transporter-expressing cells.
Competing Interests: There is no conflict of interest to declare.
(This journal is © The Royal Society of Chemistry.)
Databáze: MEDLINE
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