A novel small molecule A2A adenosine receptor agonist, indirubin-3′-monoxime, alleviates lipid-induced inflammation and insulin resistance in 3T3-L1 adipocytes

Choudhary, Saynaz A.; Bora, Nikita; Banerjee, Dipanjan; Arora, Leena; Das, Anindhya Sundar; Yadav, Rakesh; Klotz, Karl‐Norbert; Pal, Durba; Jha, Anupam Nath; Dasgupta, Suman

doi:10.1042/bcj20190251

Cited by 11 publications

(4 citation statements)

References 67 publications

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“…In the preparation of ligands, the structures of phytochemicals detected through the GC-MS technique from the methanolic leaf extract were retrieved from the PubChem database ( Choudhary et al, 2019 ) in SDF format. Afterward, the Avogadro software was used to optimize the geometry of the phytochemicals ( Snyder and Kucukkal, 2021 ).…”

Section: Methodsmentioning

confidence: 99%

Evaluation of Adenanthera pavonina-derived compounds against diabetes mellitus: insight into the phytochemical analysis and in silico assays

Rahman,

Hosen,

Faruqe

et al. 2024

Front. Mol. Biosci.

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Adenanthera pavonina is a medicinal plant with numerous potential secondary metabolites showing a significant level of antidiabetic activity. The objective of the current study was to identify potential phytochemicals from the methanolic leaf extract of Adenanthera pavonina as therapeutic agents against diabetes mellitus using GC-MS and in silico methods. The GC-MS analysis of the leaf extract revealed a total of 17 phytochemicals. Molecular docking was performed using these phytochemicals, targeting the mutated insulin receptor tyrosine kinase (5hhw), which inhibits glucose uptake by cells. Diazoprogesterone (−9.2 kcal/mol), 2,4,4,7a-Tetramethyl-1-(3-oxobutyl)octahydro-1H-indene-2-carboxylic acid (−6.9 kcal/mol), and 2-Naphthalenemethanol, decahydro-.alpha.,.alpha.,4a-trimethyl-8-methylene-, [2R-(2.alpha.,4a.alpha.,8a.beta.)] (−6.6 kcal/mol) exhibited better binding with the target protein. The ADMET analysis was performed for the top three compounds with the best docking scores, which showed positive results with no observed toxicity in the AMES test. Furthermore, the molecular dynamics study confirmed the favorable binding of Diazoprogesterone, 2,4,4,7a-Tetramethyl-1-(3-oxobutyl)octahydro-1H-indene-2-carboxylic acid and 2-Naphthalenemethanol, decahydro-.alpha.,.alpha.,4a-trimethyl-8-methylene-, [2R-(2.alpha.,4a.alpha.,8a.beta.)] with the receptor throughout the 100 ns simulation period.

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Section: Methodsmentioning

confidence: 99%

Evaluation of Adenanthera pavonina-derived compounds against diabetes mellitus: insight into the phytochemical analysis and in silico assays

Rahman,

Hosen,

Faruqe

et al. 2024

Front. Mol. Biosci.

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“…Using a combination of in silico virtual screening of potential anti-diabetic candidates and an in vitro study using an insulin-resistant model of 3T3-L1 adipocytes, Choudhary et al [ 106 ] showed that 1 prevented lipid-induced impairment of the insulin signaling pathway in adipocytes via A2A adenosine receptor activation. While compound 1 reduced lipid-induced adipocyte inflammation by inhibiting NF-κB dependent pro-inflammatory cytokine expression, it also augmented cAMP responsive element binding protein (CREB) activation, favoring an overall anti-inflammatory state [ 106 ].…”

Section: Indirubin Oxime-based Kinase Inhibitorsmentioning

confidence: 99%

Oximes: Novel Therapeutics with Anticancer and Anti-Inflammatory Potential

et al. 2021

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Oximes have been studied for decades because of their significant roles as acetylcholinesterase reactivators. Over the last twenty years, a large number of oximes have been reported with useful pharmaceutical properties, including compounds with antibacterial, anticancer, anti-arthritis, and anti-stroke activities. Many oximes are kinase inhibitors and have been shown to inhibit over 40 different kinases, including AMP-activated protein kinase (AMPK), phosphatidylinositol 3-kinase (PI3K), cyclin-dependent kinase (CDK), serine/threonine kinases glycogen synthase kinase 3 α/β (GSK-3α/β), Aurora A, B-Raf, Chk1, death-associated protein-kinase-related 2 (DRAK2), phosphorylase kinase (PhK), serum and glucocorticoid-regulated kinase (SGK), Janus tyrosine kinase (JAK), and multiple receptor and non-receptor tyrosine kinases. Some oximes are inhibitors of lipoxygenase 5, human neutrophil elastase, and proteinase 3. The oxime group contains two H-bond acceptors (nitrogen and oxygen atoms) and one H-bond donor (OH group), versus only one H-bond acceptor present in carbonyl groups. This feature, together with the high polarity of oxime groups, may lead to a significantly different mode of interaction with receptor binding sites compared to corresponding carbonyl compounds, despite small changes in the total size and shape of the compound. In addition, oximes can generate nitric oxide. This review is focused on oximes as kinase inhibitors with anticancer and anti-inflammatory activities. Oximes with non-kinase targets or mechanisms of anti-inflammatory activity are also discussed.

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“…AutoDock and AutoDockFR to get optimal receptor-ligand conformations. From the 142 compounds finally we got one molecule "indirubin-3′-monoxime" which is then followed by experimental validations [75].…”

Section: Application Examples Of Molecular Dockingmentioning

confidence: 99%

Role of Force Fields in Protein Function Prediction

Hazarika¹,

Rajkhowa²,

Jha³

2021

Homology Molecular Modeling - Perspectives and Applications

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The world today, although, has developed an elaborate health system to fortify against known and unknown diseases, it continues to be challenged by new as well as emerging, and re-emerging infectious disease threats with severity and probable fluctuations. These threats also have varying costs for morbidity and mortality, as well as for a complex set of socioeconomic outcomes. Some of these diseases are often caused by pathogens which use humans as host. In such cases, it becomes paramount responsibility to dig out the source of pathogen survival to stop their population growth. Sequencing genomes has been finessed so much in the 21st century that complete genomes of any pathogen can be sequenced in a matter of days following which; different potential drug targets are needed to be identified. Structure modeling of the selected sequences is an initial step in structure-based drug design (SBDD). Dynamical study of predicted models provides a stable target structure. Results of these in-silico techniques greatly depend on force field (FF) parameters used. Thus, in this chapter, we intend to discuss the role of FF parameters used in protein structure prediction and molecular dynamics simulation to provide a brief overview on this area.

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A novel small molecule A2A adenosine receptor agonist, indirubin-3′-monoxime, alleviates lipid-induced inflammation and insulin resistance in 3T3-L1 adipocytes

Cited by 11 publications

References 67 publications

Evaluation of Adenanthera pavonina-derived compounds against diabetes mellitus: insight into the phytochemical analysis and in silico assays

Evaluation of Adenanthera pavonina-derived compounds against diabetes mellitus: insight into the phytochemical analysis and in silico assays

Oximes: Novel Therapeutics with Anticancer and Anti-Inflammatory Potential

Role of Force Fields in Protein Function Prediction

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