Indenes and tetralenes analogues attenuates lipopolysaccharide-induced inflammation: An in-vitro and in-vivo study

Mohanty, S. R.; Gautam, Yashveer; Maurya, Anil Kumar; Negi, Arvind S.; Prakash, Om; Khan, Feroz; Bawankule, Dnyaneshwar Umrao

doi:10.1016/j.cbi.2015.12.005

Cited by 5 publications

(4 citation statements)

References 26 publications

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“…Lu et al found that LPS stimulated EGFR activation in macrophages, which regulated cytokine production and experimental colitis [25]. Deletion of EGFR in LPS-stimulated macrophages leads to increases in anti-inflammatory cytokine IL-10, which plays a role in suppressing pro-inflammatory cytokine production, resulting in protection of mice from intestinal inflammation [26]. EGFR signaling also mediates LPS-induced adhesion molecule expression and neutrophil adhesion, as evidenced in human tracheal smooth muscle cells [27].…”

Section: Discussionmentioning

confidence: 99%

Inhibition of epidermal growth factor receptor attenuates LPS-induced inflammation and acute lung injury in rats

et al. 2017

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Acute lung injury (ALI) and its severe form acute respiratory distress syndrome remain the leading cause of morbidity and mortality in intensive care units. Inhibition of epidermal growth factor receptor (EGFR) has been found to be able to reduce inflammatory response. However, it is still unclear whether EGFR inhibition can prevent ALI. This study aimed to validate the EGFR's role in ALI and investigated the effects of EGFR inhibition on lipopolysaccharides (LPS)-induced ALI in rats. In vitro, both pharmacological inhibitors (AG1478 and 451) and si-RNA silencing of EGFR significantly inhibited LPS-induced EGFR signaling activation and inflammatory response in human lung epithelial cells or macrophages. Mechanistically, LPS induced EGFR activation via TLR4 and c-Src signaling. In vivo, rat model with ALI induced by intratracheal instillation of LPS was treated by oral administration of AG1478 and 451. It was observed that AG1478 and 451 blocked the activation of EGFR signaling in lung tissue and reduced the LPS-induced infiltration of inflammatory cells, inflammatory gene expression, and lung injuries. This study demonstrates that TLR4/c-Src-dependent EGFR signaling plays an important role in LPS-induced ALI, and that EGFR may be a potential target in treating ALI.

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Section: Discussionmentioning

confidence: 99%

Inhibition of epidermal growth factor receptor attenuates LPS-induced inflammation and acute lung injury in rats

et al. 2017

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“…With the oral dose of 10 and 30 mg/kg, the animals’ survival rate were 20% and 30%, respectively. 43 These results elucidated X22 has the potential to be a candidate for reducing the mortality of sepsis.…”

Section: Discussionmentioning

confidence: 96%

A novel imidazopyridine derivative, X22, attenuates sepsis-induced lung and liver injury by inhibiting the inflammatory response in vitro and in vivo

Ge¹,

Zhang²,

Xu³

et al. 2016

DDDT

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Sepsis remains a leading cause of death worldwide. Despite years of extensive research, effective drugs to treat sepsis in the clinic are lacking. In this study, we found a novel imidazopyridine derivative, X22, which has powerful anti-inflammatory activity. X22 dose-dependently inhibited lipopolysaccharide (LPS)-induced proinflammatory cytokine production in mouse primary peritoneal macrophages and RAW 264.7 macrophages. X22 also downregulated the LPS-induced proinflammatory gene expression in vitro. In vivo, X22 exhibited a significant protection against LPS-induced death. Pretreatment or treatment with X22 attenuated the sepsis-induced lung and liver injury by inhibiting the inflammatory response. In addition, X22 showed protection against LPS-induced acute lung injury. We additionally found that pretreatment with X22 reduced the inflammatory pain in the acetic acid and formalin models and reduced the dimethylbenzene-induced ear swelling and acetic acid-increased vascular permeability. Together, these data confirmed that X22 has multiple anti-inflammatory effects and may be a potential therapeutic option in the treatment of inflammatory diseases.

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“…The 2D structures of various tetralone derivatives drawn with ChemDraw-Ultra, were transformed into 3D and geometry was cleaned using ChemBioDraw-Ultra-v12.0 (http://www.cambr idges oft.com). Energy minimization was performed withMM2/MM3 molecular mechanics parameter until achieving the lowest stable energy (<0.001 kcal/mol) [35]. The 3D chemical structure of standard drug Diclofenac (DB00586) was retrieved from the PubChem compound database at NCBI (http://www.…”

Section: Molecular Descriptors and Structure Cleaningmentioning

confidence: 99%

“…Docking study was performed with Autodock Vina v0.8 (Molecular Graphics Lab at The Scripps Research Institute, La Jolla, CA 92037, USA) with Lamarkian Genetic algorithm for grid based searching of most optimal binding pose of tetralones and Diclofenac with anti-inflammatory target TNF-α following earlier described procedures [12,35]. Bioavailability was screened through absorption, distribution, metabolism and excretion (ADME) parameters [12,35].…”

Section: Molecular Interaction and Bioavailability Studymentioning

confidence: 99%

QSAR, ADME and docking guided semi-synthesis and in vitro evaluation of 4-hydroxy-α-tetralone analogs for anti-inflammatory activity

et al. 2020

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The compound 4-hydroxy-α-tetralone (1) is major bioactive secondary metabolite of genus Ammannia (Family-Lythraceae). The compound 1 and its various derivatives are reported to possess anti-tubercular, anti-diabetic, anti-leishmanial and bioenhancing activities. A quantitative structure activity relationship (QSAR) model for predicting anti-inflammatory activity of 4-hydroxy-α-tetralone derivatives against the tumour necrosis factor (TNF)-α, a pro-inflammatory cytokine was developed by non-linear model using artificial neural network (ANN). The regression coefficient (r 2) and the leave-oneout cross-validation regression coefficient (LOO rCV 2) of the QSAR model were 0.6976 and 0.4016, respectively, while the regression coefficient (r 2) for the external set of experimental compounds was 0.835. The 4-hydroxy-α-tetralone virtual derivatives, which showed significant inhibition of TNF-α were subjected to docking and in-silico absorption, distribution, metabolism and excretion (ADME) studies and the results showed similar binding affinity and bioavailability in compliance with the standard drug, Diclofenac. Finally, in order to validate the developed QSAR model, the most and least active virtual derivatives were semi-synthesized, characterized on the basis of their 1 H and 13 C NMR spectroscopic data and in vitro tested for concentration dependent inhibition of TNF-α. The experimental results obtained, agreed well with the predicted values. Keywords QSAR • Docking • Anti-inflammatory • TNF-α • Ammannia baccifera • In vitro studies Harish C. Upadhyay and Monika Singh contributed equally to this research.

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Indenes and tetralenes analogues attenuates lipopolysaccharide-induced inflammation: An in-vitro and in-vivo study

Cited by 5 publications

References 26 publications

Inhibition of epidermal growth factor receptor attenuates LPS-induced inflammation and acute lung injury in rats

Inhibition of epidermal growth factor receptor attenuates LPS-induced inflammation and acute lung injury in rats

A novel imidazopyridine derivative, X22, attenuates sepsis-induced lung and liver injury by inhibiting the inflammatory response in vitro and in vivo

QSAR, ADME and docking guided semi-synthesis and in vitro evaluation of 4-hydroxy-α-tetralone analogs for anti-inflammatory activity

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