Inhibition and assessment of the biophysical gating properties of GluA2 and GluA2/A3 AMPA receptors using curcumin derivatives

Qneibi, Mohammad; Hamed, Othman; Natsheh, Abdel–Razzak; Fares, Oswa; Jaradat, Nidal; Emwas, Nour; AbuHasan, Qais; Al-Kerm, Rana; Al-Kerm, Rola

doi:10.1371/journal.pone.0221132

Cited by 20 publications

(6 citation statements)

References 42 publications

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“…Up to 20 μg of high-copy plasmid DNA was prepared using the QIAGEN Plasmid Mini Kit, the tubes were then centrifuged to extract the supernatant containing the plasmid DNA, ethanol was used to wash the DNA pellet, then centrifuged again and the supernatant was carefully removed as to not disturb the pellet, finally, the pellet was air-dried, and the DNA was re-dissolved in a suitable volume of buffer, (our prior study detailed the whole DNA preparation data) [ 38 ]. The flip isoform was used in all AMPAR subunits used in this investigation.…”

Section: Methodsmentioning

confidence: 99%

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α-Lipoic Acid Derivatives as Allosteric Modulators for Targeting AMPA-Type Glutamate Receptors’ Gating Modules

Qneibi

Nassar²,

Bdir³

et al. 2022

Cells

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The ionotropic glutamate receptor subtype α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) is responsible for most excitatory transmission in the brain. AMPA receptor function is altered in numerous neurological illnesses, making AMPA receptors appealing therapeutic targets for clinical intervention. Alpha-Lipoic acid (α-LA) is a naturally occurring compound, which functions as a co-factor in metabolism and energy production. α-LA is an antioxidant with various benefits in treating diabetes, including managing symptomatic diabetic neuropathy. This study will test a novel and innovative strategy to synthesize a new isomer of lipoic acid (R-LA) derivatives (bifunctional NO-donor/antioxidant) in one chemical on homomeric and heteromeric AMPA receptor subunits. We used patch-clamp electrophysiology to examine LA derivatives expressed in human embryonic kidney 293 cells (HEK293) for inhibition and changes in desensitization or deactivation rates. LA derivatives were shown to be potent antagonists of AMPA receptors, with an 8–11-fold reduction in AMPA receptor currents seen following the delivery of the compounds. Furthermore, the LA derivatives influenced the rates of desensitization and deactivation of AMPA receptors. Based on our results, especially given that α-LA is closely connected to the nervous system, we may better understand using AMPA receptors and innovative drugs to treat neurological diseases associated with excessive activation of AMPA receptors.

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Section: Methodsmentioning

confidence: 99%

“…The weighted tau (τ w ) was calculated as τ w = (τf × af) + (τs × as), where af and as are the amplitudes of the fast (τf) and slow (τs) exponential components, respectively. Our study detailed the experimental data set [ 38 , 39 , 40 ].…”

Section: Methodsmentioning

confidence: 99%

α-Lipoic Acid Derivatives as Allosteric Modulators for Targeting AMPA-Type Glutamate Receptors’ Gating Modules

Qneibi

Nassar²,

Bdir³

et al. 2022

Cells

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“…DNA preparation, cDNA transient transfection, and cell culturing of human embryonic kidney cells (HEK293) expressing the flip isoform of AMPAR subunits have been previously described. − Electrophysiological recordings took place 36–48 h after the chemical mediated transfection took place, whereby the cells were replated on coverslips coated with laminin. The highly fluorescent cells displaying the cotransfected enhanced green fluorescent protein were selected for a giga-seal for the current recording.…”

Section: Methodsmentioning

confidence: 99%

Ortho versus Meta Chlorophenyl-2,3-Benzodiazepine Analogues: Synthesis, Molecular Modeling, and Biological Activity as AMPAR Antagonists

et al. 2020

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2,3-Benzodiazepine compounds are an important family of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) antagonists that act in a noncompetitive manner. Due to the critical role of AMPARs in the synapse and various neurological diseases, significant scientific interest in elucidating the molecular basis of the function of the receptors has spiked. The analogues were synthesized to assess the functional consequence of removing the amine group of the phenyl ring, the potency and efficacy of inhibition by substituting a halogen group at the meta vs ortho position of the phenyl ring, and layout the prediction of potential drug candidates for AMPAR hyperactivation. Using the whole-cell patch-clamp technique, we assessed the effect of the derivative on the amplitude of various AMPA-type glutamate receptors and calculated the desensitization and deactivation rates before and after treatment of HEK293 cells. We noticed that the amino group is not necessary for inhibition as long as an electron-withdrawing group is placed on the meta position of the phenyl ring of BDZ. Furthermore, compound 4a significantly inhibited and affected the desensitization rate of the tested AMPARs but showed no effect on the deactivation rate. The current study paves the way to a better understanding of AMPARs and provides possible drug candidates of 2,3-BDZ different from the conventional derivatives.

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“…Previous work from our laboratory provides a methodology for the DNA preparation, cDNA transient transfection, and cell culturing of HEK293 to express AMPARs (of the flip isoform) of different subunits [ 14 – 16 ]. Two days after the chemical mediated transfection procedure, we proceeded to assess the electrophysiological recordings of the green fluorescent protein cotransfected cells.…”

Section: Methodsmentioning

confidence: 99%

Glechoma curviflora Volatile Oil from Palestine: Chemical Composition and Neuroprotective, Antimicrobial, and Cyclooxygenase Inhibitory Activities

Al‐Maharik

Jaradat

Qneibi

et al. 2020

Evidence-Based Complementary and Alternative Medicine

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The rise of the emergence of microbial resistance of antibiotics, the dangerous side effects of nonsteroidal anti-inflammatory drugs, and noncompetent medications of Alzheimer’s, Parkinson’s, and other neurodegenerative diseases prompt scientists to search for phytochemicals that could be utilized in the remedy of lethal diseases. Glechoma curviflora (Boiss.) Kuntze (Nepeta curviflora) is a medicinal herb growing in the eastern parts of the Mediterranean Sea Basin and is widely consumed as a tea. The leaves of this plant have been traditionally used for the treatment of various infectious diseases. The current research was designed to identify the chemical composition of Glechoma curviflora (Boiss.) essential oil (EO) and to assess its antibacterial, antifungal, and cyclooxygenase inhibitory activities and the biophysical gating effect on AMPA receptors. Twenty phytochemicals were identified from G. curviflora leaves and flowers EO amounting to almost 100% of the total constituents using GC-MS technique, of which 1,6-dimethylspiro[4.5]decane (27.51%) 1, caryophyllene oxide (20.08%) 2, and β-caryophyllene (18.28%) 3 were the main constituents. The biophysical properties’ effect from the plant extract on various AMPA-type receptors expressed in Human Embryonic Kidney (HEK293) cells was assessed by exploiting the whole-cell patch-clamp technique. Microdilution assay was adopted for assessing the antimicrobial property against eight virulent microbial strains whilst the cyclooxygenase inhibition effect was accomplished utilizing COX inhibitory screening colorimetric assay G. curviflora EO displayed potent activity against P. aeruginosa (MIC = 1.25 μg/mL), S. sonnei (MIC = 3.12 μg/mL), and E. coli (MIC = 1.25 μg/mL), compared with ciprofloxacin (positive control) and potent antibacterial activity against S. aureus, MRSA, S. sonnei, E. coli, and P. aeruginosa compared to Ampicillin (2nd positive control). It also showed anti-Candida (MIC = 6.25 μg/mL) and antimold (MIC = 3.125 μg/mL) activities compared with fluconazole (antifungal positive control). Likewise, our results showed an inhibition and biophysical impact of G. curviflora on all AMPARs subunits.

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Inhibition and assessment of the biophysical gating properties of GluA2 and GluA2/A3 AMPA receptors using curcumin derivatives

Cited by 20 publications

References 42 publications

α-Lipoic Acid Derivatives as Allosteric Modulators for Targeting AMPA-Type Glutamate Receptors’ Gating Modules

α-Lipoic Acid Derivatives as Allosteric Modulators for Targeting AMPA-Type Glutamate Receptors’ Gating Modules

Ortho versus Meta Chlorophenyl-2,3-Benzodiazepine Analogues: Synthesis, Molecular Modeling, and Biological Activity as AMPAR Antagonists

Glechoma curviflora Volatile Oil from Palestine: Chemical Composition and Neuroprotective, Antimicrobial, and Cyclooxygenase Inhibitory Activities

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