New fluorescent derivatives for s receptors were designed and synthesized. To achieve this purpose, a4-nitro-2,1,3-benzoxadiazole fluorescent tag was connected through a piperazine linker to a modifiedskeleton derived from selected s receptor agonists or antagonists. Compounds 5g, 7b, 7e and 7gdisplayed 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). Bindingaffinity studies revealed that compounds 5d, 5g, 7b, 7e and 7g showed no affinity towards severalreceptors including opioid, dopaminergic, serotonergic, adrenergic, muscarinic, histaminergic,N-methyl-D-aspartate (NMDA), NMDA receptor channel, or dopamine and serotonine transporters. Thefluorescent properties, cellular uptake and confocal microscopy studies on 5d suggest a potential use ofthis 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

SCHININA', BARBARA;De Guidi Guido;Catalfo Alfio;Rappazzo Giancarlo;ZUCCARELLO, ELISA;Prezzavento Orazio;Amata Emanuele;Rescifina Antonio;Marrazzo Agostino
2015

Abstract

New fluorescent derivatives for s receptors were designed and synthesized. To achieve this purpose, a4-nitro-2,1,3-benzoxadiazole fluorescent tag was connected through a piperazine linker to a modifiedskeleton derived from selected s receptor agonists or antagonists. Compounds 5g, 7b, 7e and 7gdisplayed 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). Bindingaffinity studies revealed that compounds 5d, 5g, 7b, 7e and 7g showed no affinity towards severalreceptors including opioid, dopaminergic, serotonergic, adrenergic, muscarinic, histaminergic,N-methyl-D-aspartate (NMDA), NMDA receptor channel, or dopamine and serotonine transporters. Thefluorescent properties, cellular uptake and confocal microscopy studies on 5d suggest a potential use ofthis 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/20.500.11769/43615
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