Aryl quinolinyl hydrazone derivatives as anti-inflammatory agents that inhibit TLR4 activation in the macrophages

A series of aryl 7-chloroquinolinyl hydrazone derivatives (3a-u) have been synthesized in 55–76% yield using simple reaction condition. The synthesized compounds were evaluated for their anti-inflammatory activities based on their ability to inhibit pro-inflammatory cytokine secretion from the macro...

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Bibliographic Details
Published in:European journal of pharmaceutical sciences 2019-06, Vol.134, p.102-115
Main Authors: Debnath, Utsab, Mukherjee, Suprabhat, Joardar, Nikhilesh, Sinha Babu, Santi P., Jana, Kuladip, Misra, Anup Kumar
Format: Article
Language:English
Subjects:
Animals
Anti-inflammatory agents
Anti-Inflammatory Agents - chemical synthesis
Anti-Inflammatory Agents - chemistry
Anti-Inflammatory Agents - pharmacology
Hydrazones - chemical synthesis
Hydrazones - chemistry
Interleukin-10 - metabolism
Interleukin-1beta - metabolism
Interleukin-6 - metabolism
Lipopolysaccharides
Macrophage
Macrophages - metabolism
Mice
Molecular Structure
Quinolinyl hydrazone
RAW 264.7 Cells
Signal Transduction - drug effects
Structure-Activity Relationship
Toll-like receptor 4
Toll-Like Receptor 4 - antagonists & inhibitors
Toll-Like Receptor 4 - metabolism
Transcription Factor RelA - metabolism
Tumor Necrosis Factor-alpha - metabolism
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Summary:A series of aryl 7-chloroquinolinyl hydrazone derivatives (3a-u) have been synthesized in 55–76% yield using simple reaction condition. The synthesized compounds were evaluated for their anti-inflammatory activities based on their ability to inhibit pro-inflammatory cytokine secretion from the macrophages after stimulation with lipopolysaccharide (LPS). Three compounds appeared as promising anti-inflammatory agents. The mechanism of inflammatory activity of the potent compound 3e was further investigated using a series of biochemical, molecular and microscopic techniques. Further structure activity relationship (SAR) study was carried out to validate the anti-inflammatory activities of the active compounds. Our experimental data revealed that the active moiety i.e. compound 3e majorly causes inhibition of TLR4 signaling pathway and this appears to be the novel functional attribute of this compound. [Display omitted]
ISSN:0928-0987
1879-0720
DOI:10.1016/j.ejps.2019.04.016