Uttam Pal - Synthesis and bio-evaluation of human macrophage migration inhibitory factor inhibitor to develop anti-inflammatory agent

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      Alam, Athar, Pal, Chinmay, Goyal, Manish, Kundu, Milan Kumar,   Kumar, Rahul, Iqbal, Mohd Shameel, Dey, Sumanta, Bindu, Samik,   Sarkar, Souvik, Pal, Uttam, Maiti, Nakul C, Adhikari, Susanta,   Bandyopadhyay, Uday 19 (24) 7365-7373

      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-κB   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.

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