New fluorescent derivatives for s receptors were designed and synthesized. To achieve this purpose, a 4-nitro-2,1,3-benzoxadiazole fluorescent tag was connected through a piperazine linker to a modified skeleton derived from selected s receptor agonists or antagonists. Compounds 5g, 7b, 7e and 7g displayed high s1 affinity and low s1/s2 selectivity (Kis1 ranging from 31.6 nM to 48.5 nM, Kis1/s2 ¼ 5–18), while compound 5d exhibited high s2 affinity and selectivity (Kis2 ¼ 56.8 nM, Kis1 > 5000 nM). Binding affinity studies revealed that compounds 5d, 5g, 7b, 7e and 7g showed no affinity towards several receptors including opioid, dopaminergic, serotonergic, adrenergic, muscarinic, histaminergic, N-methyl-D-aspartate (NMDA), NMDA receptor channel, or dopamine and serotonine transporters. The fluorescent properties, cellular uptake and confocal microscopy studies on 5d suggest a potential use of this probe to further clarify the molecular role of s2 receptor subtypes in normal and cancer cells.

4-Nitro-2,1,3-benzoxadiazole derivatives as potential fluorescent sigma receptor probes

COLABUFO, Nicola Antonio;CONTINO, MARIALESSANDRA;NISO, MAURO;PERRONE, MARIA GRAZIA;
2015

Abstract

New fluorescent derivatives for s receptors were designed and synthesized. To achieve this purpose, a 4-nitro-2,1,3-benzoxadiazole fluorescent tag was connected through a piperazine linker to a modified skeleton derived from selected s receptor agonists or antagonists. Compounds 5g, 7b, 7e and 7g displayed high s1 affinity and low s1/s2 selectivity (Kis1 ranging from 31.6 nM to 48.5 nM, Kis1/s2 ¼ 5–18), while compound 5d exhibited high s2 affinity and selectivity (Kis2 ¼ 56.8 nM, Kis1 > 5000 nM). Binding affinity studies revealed that compounds 5d, 5g, 7b, 7e and 7g showed no affinity towards several receptors including opioid, dopaminergic, serotonergic, adrenergic, muscarinic, histaminergic, N-methyl-D-aspartate (NMDA), NMDA receptor channel, or dopamine and serotonine transporters. The fluorescent properties, cellular uptake and confocal microscopy studies on 5d suggest a potential use of this probe to further clarify the molecular role of s2 receptor subtypes in normal and cancer cells.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11586/139551
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