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 probe6demonstrated high binding affinity (Ki= 43 nM) for NET and an overall selectivity compared to the other transporters for dopamine (DAT;Ki= 1540 nM) and serotonin (SERT;Ki= 785 nM) in competitive radioligand binding assays. Using confocal microscopy, compound6was shown to stain both NET and SERT, but not DAT, at low nanomolar concentrations, in transporter-expressing cells.

Illuminating the norepinephrine transporter: fluorescent probes based on nisoxetine and talopram / G.A. Camacho-Hernandez, A. Casiraghi, D. Rudin, D. Luethi, T.C. Ku, D.A. Guthrie, V. Straniero, E. Valoti, G.J. Schutz, H.H. Sitte, A.H. Newman. - In: RSC MEDICINAL CHEMISTRY. - ISSN 2632-8682. - 12:7(2021 Jul 01), pp. 1174-1186. [10.1039/d1md00072a]

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

A. Casiraghi
Secondo
;
V. Straniero;E. Valoti;
2021

Abstract

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 probe6demonstrated high binding affinity (Ki= 43 nM) for NET and an overall selectivity compared to the other transporters for dopamine (DAT;Ki= 1540 nM) and serotonin (SERT;Ki= 785 nM) in competitive radioligand binding assays. Using confocal microscopy, compound6was shown to stain both NET and SERT, but not DAT, at low nanomolar concentrations, in transporter-expressing cells.
Settore CHIM/08 - Chimica Farmaceutica
9-giu-2021
Article (author)
File in questo prodotto:
File Dimensione Formato  
RSC_MedChem_2021.pdf

accesso riservato

Tipologia: Publisher's version/PDF
Dimensione 2.64 MB
Formato Adobe PDF
2.64 MB Adobe PDF   Visualizza/Apri   Richiedi una copia
Pubblicazioni consigliate

Caricamento pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/870160
Citazioni
  • ???jsp.display-item.citation.pmc??? 2
  • Scopus 2
  • ???jsp.display-item.citation.isi??? 1
social impact