Characterisation of a novel coumarin-based fluorescent probe for monitoring nitric oxide production in macrophages

Sadek, Maiada M.; Olia, Mina Barzegar Amiri; Nowell, Cameron J.; Barlow, Νicholas; Schiesser, Carl H.; Nicholson, Sandra E.; Norton, Raymond S.

doi:10.1016/j.bmc.2017.08.054

Cited by 16 publications

(9 citation statements)

References 23 publications

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“…As shown in Figure 1B,adecrease in fluorescencei ntensity was observedu pon the introduction of bromine and iodine atoms (compounds 10 and 11,r espectively),c onsistent with the heavy-atom effect observed for relatedf luorescent systems. [7,10] Replacement of the -NH 2 group with an -NMe 2 unit furtherd ecreased the fluorescence intensity (compounds [12][13][14]. Thisi si nc ontrastt oo ur previouso bservation for compounds 1-8,f or which ar emarkable increase in fluorescence intensity was observed when an -NMe 2 group was introduced in place of -NH 2 at the 4-positiono fthe naphthalimide moiety.…”

Section: Resultsmentioning

confidence: 91%

“…However, when the coumarin‐based compounds 25 and 26 were used for cellular uptake studies, a 24 % uptake of compound 25 was increased to 94 % for compound 26 , indicating that the 2,6‐diiodoanisole moiety is very effective in increasing the membrane transport of coumarin‐based fluorescent molecules. Due to their excellent light stability and low toxicity, coumarin derivatives have been extensively used as fluorescent probes for the detection of nitric oxide, hydrogen peroxide, and various metal ions . The present study suggests that halogen atoms may be introduced to improve the cellular uptakes of such probes.…”

Section: Resultsmentioning

confidence: 99%

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Halogen‐Mediated Membrane Transport: An Efficient Strategy for the Enhancement of Cellular Uptake of Synthetic Molecules

Ungati

Govindaraj

Nair

et al. 2019

Chemistry A European J

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The poor uptake of fluorescent probesa nd therapeutics by mammalian cells is am ajor concern in biological applicationsr anging from fluorescencei maging to drug delivery in living cells. Although gaseous molecules such as oxygen and carbon dioxide, hydrophobic substances such as benzene, and small polar but uncharged molecules such as water ande thanolc an cross the cell plasma membrane by simple passived iffusion, many synthetic as well as biological molecules require specific membrane transporters and channel proteins that control the traffic of these molecules into and out of the cell. This work reports that the introduction of halogen atoms into as eries of fluorescent molecules remarkably enhances their cellular uptake, and that their trans-port can be increased to more than 95 %b yi ntroducing two iodine atoms at appropriate positions. The nature of the fluorophore does not play am ajor role in the cellular uptake when iodine atoms are presenti nt he molecules, as compoundsb earing naphthalimide, coumarin, BODIPY, and pyrene moieties shows imilar uptakes.I nterestingly,t he introduction of am aleimide-based fluorophore bearing two hydroxyethylthio moieties allows the molecules to cross the plasma and nuclear membranes, and the presence of iodine atoms furthere nhances the transport across both membranes. Overall, this study provides ag eneral strategy for enhancingt he uptake of organic molecules by mammalian cells.

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Section: Resultsmentioning

confidence: 91%

Section: Resultsmentioning

confidence: 99%

Halogen‐Mediated Membrane Transport: An Efficient Strategy for the Enhancement of Cellular Uptake of Synthetic Molecules

Ungati

Govindaraj

Nair

et al. 2019

Chemistry A European J

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“…Previous studies testing different NO sensors have predominately used the murine macrophage RAW264 cell line, which report sensor uptake in undifferentiated macrophages via microscopy. These studies have not demonstrated parallel changes in iNOS activity or reported changes in sensor uptake in the presence of inflammatory stimuli [ 11 , 24 ]. These reports and our observations suggest a cell-species dependent effect in which inflammation has varying effects on Ru-NO uptake into macrophages.…”

Section: Discussionmentioning

confidence: 99%

Biological Sensing of Nitric Oxide in Macrophages and Atherosclerosis Using a Ruthenium-Based Sensor

et al. 2022

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Macrophage-derived nitric oxide (NO) plays a critical role in atherosclerosis and presents as a potential biomarker. We assessed the uptake, distribution, and NO detection capacity of an irreversible, ruthenium-based, fluorescent NO sensor (Ru-NO) in macrophages, plasma, and atherosclerotic plaques. In vitro, incubation of Ru-NO with human THP1 monocytes and THP1-PMA macrophages caused robust uptake, detected by Ru-NO fluorescence using mass-cytometry, confocal microscopy, and flow cytometry. THP1-PMA macrophages had higher Ru-NO uptake (+13%, p < 0.05) than THP1 monocytes with increased Ru-NO fluorescence following lipopolysaccharide stimulation (+14%, p < 0.05). In mice, intraperitoneal infusion of Ru-NO found Ru-NO uptake was greater in peritoneal CD11b+F4/80+ macrophages (+61%, p < 0.01) than CD11b+F4/80− monocytes. Infusion of Ru-NO into Apoe−/− mice fed high-cholesterol diet (HCD) revealed Ru-NO fluorescence co-localised with atherosclerotic plaque macrophages. When Ru-NO was added ex vivo to aortic cell suspensions from Apoe−/− mice, macrophage-specific uptake of Ru-NO was demonstrated. Ru-NO was added ex vivo to tail-vein blood samples collected monthly from Apoe−/− mice on HCD or chow. The plasma Ru-NO fluorescence signal was higher in HCD than chow-fed mice after 12 weeks (37.9%, p < 0.05). Finally, Ru-NO was added to plasma from patients (N = 50) following clinically-indicated angiograms. There was lower Ru-NO fluorescence from plasma from patients with myocardial infarction (−30.7%, p < 0.01) than those with stable coronary atherosclerosis. In conclusion, Ru-NO is internalised by macrophages in vitro, ex vivo, and in vivo, can be detected in atherosclerotic plaques, and generates measurable changes in fluorescence in murine and human plasma. Ru-NO displays promising utility as a sensor of atherosclerosis.

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“…The cellular uptake studies with the coumarin‐based compounds 22 and 23 indicated that the marginal uptake of 24 % for compound 22 was increased remarkably to 94 % for compound 23 , indicating that 2,6‐diiodoanisole can be attached successfully to coumarin‐based fluorescent molecules to enhance their cellular uptake for fluorescence imaging. It should be noted that coumarin derivatives are being used extensively as fluorescent probes for the detection of nitric oxide, hydrogen peroxide, and various metal ions…”

Section: Cellular Uptake Of Halogen Compoundsmentioning

confidence: 99%

Directing Traffic: Halogen‐Bond‐Mediated Membrane Transport

Govindaraj

Ungati

Jakka

et al. 2019

Chemistry A European J

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The plasma membrane regulates the transport of molecules into the cell. Small hydrophobic molecules can diffuse directly across the lipid bilayer. However, larger molecules require specific transporters for their entry into the cell. Regulating the cellular entry of small molecules and proteins is a challenging task. The introduction of halogen, particularly iodine, to small molecules and proteins is emerging to be a promising strategy to improve the cellular uptake. Recent studies reveal that a simple substitution of hydrogen atom with iodine not only increases the cellular uptake, but also regulates the membrane transport. The strong halogen‐bond‐forming ability of iodine atoms plays a crucial role in the transport and the introduction of iodine may provide an efficient strategy for studying membrane activity and cellular functions and improving the delivery of therapeutic agents. This Concept article does not provide a comprehensive picture of membrane transport but highlights halogen‐substitution as a novel strategy for understanding and regulating the cell‐membrane traffic.

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Characterisation of a novel coumarin-based fluorescent probe for monitoring nitric oxide production in macrophages

Cited by 16 publications

References 23 publications

Halogen‐Mediated Membrane Transport: An Efficient Strategy for the Enhancement of Cellular Uptake of Synthetic Molecules

Halogen‐Mediated Membrane Transport: An Efficient Strategy for the Enhancement of Cellular Uptake of Synthetic Molecules

Biological Sensing of Nitric Oxide in Macrophages and Atherosclerosis Using a Ruthenium-Based Sensor

Directing Traffic: Halogen‐Bond‐Mediated Membrane Transport

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