Insights into the Identification of p38-alpha Mitogen activated Protein Kinase against Pyridazinopyridinone Derivatives in the Treatment of Rheumatoid Arthritis

Mahendran, Ratha; Jeyabasker, Suganya; Francis, Astral; Manoharan, Sharanya

doi:10.5958/0974-360x.2017.00507.8

Cited by 5 publications

(2 citation statements)

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“…Another important factor in the development of RA being explored as a potential therapeutic target is modulation of proinflammatory signaling pathways, including the nuclear factor κB (NF‐κB) and p38/mitogen‐activated protein kinase (MAPK) proinflammatory pathways, by targeting upstream regulators of pathway activation. Of these, sustained activation of the NF‐κB pathway is considered to be of critical importance to the pathogenesis of RA . Recruitment of immune cells to the pannus further induces inflammation and promotes the release of cytokines and chemokines.…”

Section: Introductionmentioning

confidence: 99%

Exenatide ameliorates inflammatory response in human rheumatoid arthritis fibroblast‐like synoviocytes

Tao

Wang

et al. 2019

IUBMB Life

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Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease of unknown etiology characterized by degradation of cartilage and bone, accompanied by unimpeded proliferation of synoviocytes of altered phenotype. In the present study, we investigated the involvement of the glucagon‐like peptide 1 (GLP‐1) receptor on human fibroblast‐like synoviocytes (FLS) in the pathogenesis of RA using the selective GLP‐1 agonist exenatide, a licensed drug used for the treatment of type 2 diabetes. Our results indicate that exenatide may play a role in regulating tumor necrosis factor‐α‐induced mitochondrial dysfunction by increasing mitochondrial membrane potential, oxidative stress by reducing the production of reactive oxygen species, the expression of NADPH oxidase 4, expression of matrix metalloproteinase (MMP)‐3 and MMP‐13, release of proinflammatory cytokines including interleukin‐1β (IL‐1β), IL‐6, monocyte chemoattractant protein‐1, and high‐mobility group protein 1, as well as activation of the p38/nuclear factor of κ light polypeptide gene enhancer in B‐cells inhibitor, α/nuclear factor κB signaling pathway in primary human RA FLS. These positive results indicate that exenatide may have potential as a therapeutic agent for the treatment and prevention of RA. © 2019 IUBMB Life, 9999(9999):1–9, 2019

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Section: Introductionmentioning

confidence: 99%

Exenatide ameliorates inflammatory response in human rheumatoid arthritis fibroblast‐like synoviocytes

Tao

Wang

et al. 2019

IUBMB Life

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“…Prior to molecular docking, the structures of all test compounds 1-14 were optimized in the semi-empirical PM3 method 54 using the ArgusLab 4.0.1 software package. [55][56][57][58][59][60][61][62][63][64]…”

Section: Molecular Docking Studies Ligand Preparationmentioning

confidence: 99%

Synthesis, Anti-Inflammatory Activity and Molecular Docking Studies of 1,4,5,6-Tetrahydropyrimidine-2-Carboxamides

et al. 2020

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Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most commonly used drugs in the world. The widespread use of NSAIDs is associated with a number of serious side effects and complications observed for both selective and non-selective COX inhibitors. Therefore, the search for new COX inhibitors, which along with their effectiveness will have minimal side effects, is a very important and urgent task. Methods: This work studied the synthesis of new 1,4,5,6-tetrahydropyrimidine-2-carboxamides based on the reaction of 2-morpholin-4-yl-N-(het)aryl-2-thioxoacetamides with 1,3-diaminopropane. All obtained compounds were tested for anti-inflammatory activity in vitro and in silico conditions. All synthesized 1,4,5,6-tetrahydropyrimidine-2-carboxamides were tested for influence on the course of the exudative phase of the inflammatory process based on the carrageenan model of paw edema of laboratory nonlinear heterosexual white rats weighing 220-250 g, using Diclofenac as a reference. Optimization of the geometry of the studied structures and molecular docking was carried out using the ArgusLab 4.0.1 software package. Results: The target products were obtained with yields of 71-98% and easily isolated from the reaction mixture. The best anti-inflammatory activity was found in N-(4-chlorophenyl)-1,4,5,6-tetrahydropyrimidine-2-carboxamide and in N-[4-chloro-3-(trifluoromethyl)phenyl]-1,4,5,6-tetrahydropyrimidine-2-carboxamide, suppression of the inflammatory response was 46.7 and 46.4%, respectively. The results of molecular docking with COX-1 and COX-2 enzymes were in good agreement with the experimental data, R2 ˃ 0.92 and R2 ˃ 0.83, respectively. Conclusion: The compounds under study were shown to be promising as potential anti-inflammatory agents.

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In-silico Molecular Docking of Coumarin and Naphthalene Derivatives from Pyrenacantha volubilis with the Pathological Mediators of Rheumatoid Arthritis

Anjali¹,

Vimalavathini²

2021

RJPT

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Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease which mainly targets synovial membrane during its disease pathogenesis. Available therapeutic drugs for the treatment of RA provide only symptomatic relief and are associated with severe side effects. Herbal plants comprise many active biological compounds that cure the disease with minimal adverse effects. Pyrenacantha volubilis is a climber and member of Icacinaceae family. Gas chromatography- mass spectrometry (GC-MS) analysis of ethanolic extracts of leaves of Pyrenacantha volubilis (EEPV) reveals the presence of 2-isopropyl-5-methylcyclohexyl 3-(1-(4- chlorophenyl)-3-oxobutyl)-coumarin-4-yl carbonate and 1-naphthalenepropanol, alpha-ethyldecahydro-5- (hydroxymethyl)-alpha,5,8A-trimethyl-2-methyl phytoconstitutents. Hence these compounds were docked with various pathological mediators of RA using Autodock 4.2. The docking results unveils that these compounds had better binding energy against inflammatory, oxidative stress and receptor for advanced glycation end products (RAGE) mediators that plays a pivotal role in the progression of RA. However, this study warrants further in- vitro and in-vivo studies to be carried out to establish the anti-inflammatory and anti-arthritic activity of selected phytoconstitutents.

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Insights into the Identification of p38-alpha Mitogen activated Protein Kinase against Pyridazinopyridinone Derivatives in the Treatment of Rheumatoid Arthritis

Cited by 5 publications

References 0 publications

Exenatide ameliorates inflammatory response in human rheumatoid arthritis fibroblast‐like synoviocytes

Exenatide ameliorates inflammatory response in human rheumatoid arthritis fibroblast‐like synoviocytes

Synthesis, Anti-Inflammatory Activity and Molecular Docking Studies of 1,4,5,6-Tetrahydropyrimidine-2-Carboxamides

In-silico Molecular Docking of Coumarin and Naphthalene Derivatives from Pyrenacantha volubilis with the Pathological Mediators of Rheumatoid Arthritis

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