Effect of prednisolone on the primary immunologic response

Uteshev, L. S.; Пинегин, Б В; Kalinkovich, Alexander; Лебедев, В. В.

doi:10.1007/bf00808983

Cited by 2 publications

(2 citation statements)

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“…The α7 nicotinic acetylcholine receptor (nAChR) is widely expressed in neuronal (central and autonomic system) and non‐neuronal cells (immune cells, adipocytes, osteoblasts, lung cells, skin cells) and is characterized by rapid channel activation and inactivation kinetics, low probability of opening, and high calcium permeability relative to the other nAChR subtypes . In the last decade, the homopentameric α7 nAChR has been extensively studied as regards its structural features, the heterogeneity and complexity of its functional coupling, and the crucial roles it plays in cognitive and attentional processes, sensory gating, neuroprotection, neurogenesis, and cholinergic control of inflammation .…”

Section: Introductionmentioning

confidence: 99%

Identification of α7 Nicotinic Acetylcholine Receptor Silent Agonists Based on the Spirocyclic Quinuclidine‐Δ²‐Isoxazoline Scaffold: Synthesis and Electrophysiological Evaluation

et al. 2017

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Compound 11 (3-(benzyloxy)-1′-methyl-1′-azonia-4H-1′-azaspiro[isoxazole-5,3′-bicyclo[2.2.2]octane] iodide) was selected from a previous set of nicotinic ligands as a suitable model ligand for the design of new silent agonists of α7 nAChRs. Silent agonists evoke little or no channel activation but can induce the α7 desensitized Ds state, sensitive to a type II positive allosteric modulator (PAM) such as PNU-120596. Introduction of meta-substituents into the benzyloxy moiety of 11 led to the two sets of tertiary amines and quaternary ammonium salts based on the spirocyclic quinuclidinyl-Δ2-isoxazoline scaffold. Electrophysiological assays performed on Xenopus laevis oocytes expressing human α7 nAChRs highlighted four compounds which are endowed with a significant silent agonism profile. The structure-activity relationships on this group of analogs put in evidence the crucial role of the positive charge at the quaternary quinuclidine nitrogen. Moreover, the present study indicates that meta-substituents, in particular halogens, on the benzyloxy substructure direct specific interactions able to stabilize a desensitized conformational state of the receptor and induce silent activity.

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Section: Introductionmentioning

confidence: 99%

Identification of α7 Nicotinic Acetylcholine Receptor Silent Agonists Based on the Spirocyclic Quinuclidine‐Δ²‐Isoxazoline Scaffold: Synthesis and Electrophysiological Evaluation

et al. 2017

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“…Structurally, it is a homomeric protein with a ligand‐gated ion channel with five sites for acetylcholine binding [13] . When an agonist binds to the binding domain, there is an increase in the permeability of calcium, [14] which has been detected to protect neurons from death in a variety of toxicity models [15] . Agonists of α7nAChR can cross blood‐brain barriers [16] .…”

Section: Introductionmentioning

confidence: 99%

Molecular Docking and Dynamic Simulation to Identify α7nAChR Binding Affinity of Flavonoids for the Treatment of Alzheimer's Disease

Singh

Goyal

Agrawal

2023

Chemistry & Biodiversity

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Background: Alpha-7-nicotinic acetylcholine receptor (α7nAChR), a ligand-gated ion channel is one of the important parts of the cholinergic pathway in the brain and has a remarkable role in Alzheimer's disease (AD). It has been documented that the modulation of α7nAChR with the help of phytoconstituent can be helpful in the treatment of AD. Method: The binding efficacy of fifty flavonoids was evaluated for human α7nAChR using molecular docking. The best two flavonoids shortlisted from docking analysis were then subjected to molecular dynamic simulations for 100 ns to analyze conformational binding stability with the target protein. Further, the druggability of the selected flavonoids was checked using in silico ADMET studies. Result:The top two flavonoids selected based on binding affinity toward the binding site of α7nAChR from molecular docking were amentoflavone (-9.1 kcal/mol) and gallocatechin (-8.8 kcal/mol). The molecular dynamics simulation revealed that amentoflavone and gallocatechin have a stable state during overall simulation time, lesser root mean deviation (RMSD) and root mean square fluctuation (RMSF), and complex of both compounds with protein is stable until 100 ns. Conclusion:The two flavonoids amentoflavone and gallocatechin are potential lead molecules that could be utilized as effective agonists of α7nAChR to combat Alzheimer's disease. Future in vitro and in vivo analyses are required to confirm their effectiveness.

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Effect of prednisolone on the primary immunologic response

Cited by 2 publications

References 3 publications

Identification of α7 Nicotinic Acetylcholine Receptor Silent Agonists Based on the Spirocyclic Quinuclidine‐Δ²‐Isoxazoline Scaffold: Synthesis and Electrophysiological Evaluation

Identification of α7 Nicotinic Acetylcholine Receptor Silent Agonists Based on the Spirocyclic Quinuclidine‐Δ²‐Isoxazoline Scaffold: Synthesis and Electrophysiological Evaluation

Molecular Docking and Dynamic Simulation to Identify α7nAChR Binding Affinity of Flavonoids for the Treatment of Alzheimer's Disease

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Effect of prednisolone on the primary immunologic response

Cited by 2 publications

References 3 publications

Identification of α7 Nicotinic Acetylcholine Receptor Silent Agonists Based on the Spirocyclic Quinuclidine‐Δ2‐Isoxazoline Scaffold: Synthesis and Electrophysiological Evaluation

Identification of α7 Nicotinic Acetylcholine Receptor Silent Agonists Based on the Spirocyclic Quinuclidine‐Δ2‐Isoxazoline Scaffold: Synthesis and Electrophysiological Evaluation

Molecular Docking and Dynamic Simulation to Identify α7nAChR Binding Affinity of Flavonoids for the Treatment of Alzheimer's Disease

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Identification of α7 Nicotinic Acetylcholine Receptor Silent Agonists Based on the Spirocyclic Quinuclidine‐Δ²‐Isoxazoline Scaffold: Synthesis and Electrophysiological Evaluation

Identification of α7 Nicotinic Acetylcholine Receptor Silent Agonists Based on the Spirocyclic Quinuclidine‐Δ²‐Isoxazoline Scaffold: Synthesis and Electrophysiological Evaluation