Fluorescent mimics of 5-hydroxytryptamine based on N-alkylated derivatives of 6-hydroxycarbostyril

Micotto, Teresa L.; Brown, Adrienne S.; Wilson, James N.

doi:10.1039/b917578d

Cited by 15 publications

(10 citation statements)

References 18 publications

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“…It should point out that bromo can also be tolerated in the reaction conditions. Therefore, a difluoromethylene analogue of fluorescent marker 5c can be prepared in one step with high efficiency . The extension of this method to 1-methyl-2-pyridone also led to the corresponding product in moderate yield.…”

Section: Resultsmentioning

confidence: 99%

Visible-Light-Induced Direct Difluoroalkylation of Uracils, Pyridinones, and Coumarins

Kong

et al. 2017

J. Org. Chem.

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An efficient and general method for the synthesis of difluoroalkylated uracils, pyridinones, and coumarins through visible-light-induced reaction with commercial materials is developed. The strategy proceeds with high efficiency under mild reaction conditions and shows excellent functional group compatibility, even toward bromide and hydroxyl group, thus demonstrates high potent application in a late-stage fluoroalkylation. Moreover, the difluoroalkylated products can be further transformed to a diverse variety of difluoroalkylated heterocycles, including molecules of potential biological activity.

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Section: Resultsmentioning

confidence: 99%

Visible-Light-Induced Direct Difluoroalkylation of Uracils, Pyridinones, and Coumarins

Kong

et al. 2017

J. Org. Chem.

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“…Brains were isolated from e19 chick embryos and plated on 96-well plates following a previously reported procedure. 18 Plates incubate for 72 h before screening. For the initial screening, fluorescent probes were added in 200 mL neuronal media (NM, Sciencell 1521 containing basal medium, neuronal growth supplement, and penicillin/streptomycin supplement) to obtain final concentrations of 100 mM and incubated for 10 min.…”

Section: Microwell Plate Preparation and Microwell Plate Assaysmentioning

confidence: 99%

Fluorescent neuroactive probes based on stilbazolium dyes

et al. 2011

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A set of spectrally diverse stilbazolium dyes was identified in an uptake assay using cultured brainstem and cerebellum cells isolated from e19 chicks. Pretreatment of cells with indatraline, a monoamine reuptake inhibitor, allowed identification of dyes that may interact with monoamine transporters. Two structurally related, yet spectrally segregated, probes, (E)-1-methyl-4-[2-(2-naphthalenyl)ethenyl]-pyridinium iodide (NEP+, 3A) and (E)-4-[2-(6-hydroxy-2-naphthalenyl)ethenyl]-1-methyl-pyridinium iodide (HNEP+, 4A), were selected and further investigated using HEK-293 cells selectively expressing dopamine, norepinephrine or serotonin transporters. HNEP+ was selectively accumulated via catecholamine transporters, with the norepinephrine transporter (NET) giving the highest response; NEP+ was not transported, though possible binding was observed. The alternate modes of interaction enable the use of NEP+ and HNEP+ to image distinct cell populations in live brain tissue explants. The preference for HNEP+ accumulation via NET was confirmed by imaging uptake in the absence and presence of desipramine, a norepinephrine reuptake inhibitor.

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“…Fluorescent SERT substrates have been developed based on the neurotoxin, MPP+ (4-phenyl- N -methylpyridinium), − including ASP+ (4-(4-dimethylaminostyryl)-1-methylpyridinium) − and APP+ (4-(4-dimethylamino)phenyl-1-methylpyridinium), , the latter of which is also a substrate for VMAT2. While these compounds offer some advantages over native 5-HT, particularly increased fluorescence, they also bind other intracellular organelles and are highly solvatochromic, which makes these probes poorly suited to measure the release of synaptic vesicle content from 5-HT neurons. , Additional prototypes of 5-HT fluorescent mimics have been reported but without rigorous characterization at SERT . These problems were resolved with 5,7-dihydroxytryptamine, a more fluorescent, pH-sensitive analog of 5-HT, which can be used to study vesicular packaging and release in 5-HT neurons via two-photon excitation with an improved signal-to-noise ratio .…”

Section: Introductionmentioning

confidence: 99%

Toward Serotonin Fluorescent False Neurotransmitters: Development of Fluorescent Dual Serotonin and Vesicular Monoamine Transporter Substrates for Visualizing Serotonin Neurons

Henke

Kovalyova

Dunn

et al. 2017

ACS Chem. Neurosci.

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Ongoing efforts in our laboratories focus on design of optical reporters known as fluorescent false neurotransmitters (FFNs) that enable the visualization of uptake into, packaging within, and release from individual monoaminergic neurons and presynaptic sites in the brain. Here, we introduce the molecular probe FFN246 as an expansion of the FFN platform to the serotonergic system. Combining the acridone fluorophore with the ethylamine recognition element of serotonin, we identified FFN54 and FFN246 as substrates for both the serotonin transporter and the vesicular monoamine transporter 2 (VMAT2). A systematic structure-activity study revealed the basic structural chemotype of aminoalkyl acridones required for serotonin transporter (SERT) activity and enabled lowering the background labeling of these probes while maintaining SERT activity, which proved essential for obtaining sufficient signal in the brain tissue (FFN246). We demonstrate the utility of FFN246 for direct examination of SERT activity and SERT inhibitors in 96-well cell culture assays, as well as specific labeling of serotonergic neurons of the dorsal raphe nucleus in the living tissue of acute mouse brain slices. While we found only minor FFN246 accumulation in serotonergic axons in murine brain tissue, FFN246 effectively traces serotonin uptake and packaging in the soma of serotonergic neurons with improved photophysical properties and loading parameters compared to known serotonin-based fluorescent tracers.

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Fluorescent mimics of 5-hydroxytryptamine based on N-alkylated derivatives of 6-hydroxycarbostyril

Abstract: Fluorescent probes based on a 6-hydroxycarbostyril core accumulate inside neurons and astroglia in the absence of a serotonin uptake inhibitor.

Cited by 15 publications

References 18 publications

Visible-Light-Induced Direct Difluoroalkylation of Uracils, Pyridinones, and Coumarins

Visible-Light-Induced Direct Difluoroalkylation of Uracils, Pyridinones, and Coumarins

Fluorescent neuroactive probes based on stilbazolium dyes

Toward Serotonin Fluorescent False Neurotransmitters: Development of Fluorescent Dual Serotonin and Vesicular Monoamine Transporter Substrates for Visualizing Serotonin Neurons

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