Record Details

Synthesis and Bio-Evaluation of Human Macrophage Migration Inhibitory Factor Inhibitor to Develop Anti-Inflammatory Agent

EPrints@IICB

View Archive Info
 
 
Field Value
 
Title Synthesis and Bio-Evaluation of Human Macrophage Migration Inhibitory Factor Inhibitor to Develop Anti-Inflammatory Agent
 
Creator Alam, Athar
Pal, Chinmay
Goyal, Manish
Kundu, Milan Kumar
Kumar, Rahul
Iqba, Mohd Shameel
Dey, Sumanta
Bindu, Samik
Sarkar, Souvik
Pal, Uttam
Maiti, Nakul Chandra
Adhikari, Susanta
Bandyopadhyay, Uday
 
Subject Infectious Diseases and Immunology
 
Description Macrophage migration inhibitory factor (MIF), a pro-inflammatory cytokine, is involved in the development
of an array of inflammatory disorders including rheumatoid arthritis, inflammatory bowel disease,
psoriasis, multiple sclerosis and sepsis. The synthesis of MIF-inhibitor is a rationale approach to develop
novel anti-inflammatory agent to treat multitude of inflammatory diseases. In this work, we have synthesized
and evaluated MIF-inhibitory activity of a series of small molecules containing isoxazoline skeleton.
Mode of binding of this inhibitor to human MIF (huMIF) was determined by docking studies. The synthesized
molecules inhibit tautomerase activity of huMIF. The anti-inflammatory activity of the most active
inhibitor, 4-((3-(4-hydroxy-3-methoxyphenyl)-4, 5-dihydroisoxazol-5-yl) methoxy) benzaldehyde (4b)
was evaluated against huMIF-induced inflammation in a cellular model (RAW 264.7 cell). Compound
4b significantly inhibits huMIF-mediated NF-jB translocation to the nucleus, up-regulation of inducible
nitric oxide synthase and nitric oxide production in RAW 264.7 cell which are the markers for inflammation.
The compound 4b is not cytotoxic as evident from cell viability assay. Hence, the compound 4b has
potential to be a novel anti-inflammatory agent.
 
Publisher Elsevier
 
Date 2011
 
Type Article
PeerReviewed
 
Format application/pdf
 
Identifier http://www.eprints.iicb.res.in/1234/1/BIOORGANIC_%26_MEDICINAL_CHEMISTRY__19(24)7365%2D7373_;2011[1].pdf
Alam, Athar and Pal, Chinmay and Goyal, Manish and Kundu, Milan Kumar and Kumar, Rahul and Iqba, Mohd Shameel and Dey, Sumanta and Bindu, Samik and Sarkar, Souvik and Pal, Uttam and Maiti, Nakul Chandra and Adhikari, Susanta and Bandyopadhyay, Uday (2011) Synthesis and Bio-Evaluation of Human Macrophage Migration Inhibitory Factor Inhibitor to Develop Anti-Inflammatory Agent. Bioorganic & Medicinal Chemistry, 19 (24). pp. 7365-7373.
 
Relation http://dx.doi.org/10.1016/j.bmc.2011.10.056
http://www.eprints.iicb.res.in/1234/