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

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.

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    Abstract

    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.

    Item Type: Article
    URI: http://www.eprints.iicb.res.in/id/eprint/1234
    Subjects: Infectious Diseases and Immunology
    Divisions: Indian Institute of Chemical Biology
    Depositing User: Ms Sutapa Ganguly
    Date Deposited: 16 Jan 2012 14:14
    Last Modified: 22 Jan 2013 12:11
    Official URL: http://dx.doi.org/10.1016/j.bmc.2011.10.056
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