Synthesis and bio-evaluation of human macrophage migration inhibitory factor inhibitor to develop anti-inflammatory agent |
| |
Authors: | 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 |
| |
Institution: | aDepartment of Infectious Diseases and Immunology, Indian Institute of Chemical Biology, 4 Raja S. C. Mullick Road, Jadavpur, Kolkata 700 032, West Bengal, India;bDepartment of Chemistry, University of Burdwan, Golapbag, Burdwan 713 104, West Bengal, India;cDepartment of Structural Biology & Bio-Informatics Division, Indian Institute of Chemical Biology, 4 Raja S. C. Mullick Road, Jadavpur, Kolkata 700 032, West Bengal, India;dDepartment of Chemistry, University of Calcutta, 92, A. P. C. Road, Kolkata 700 009, West Bengal, India |
| |
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. |
| |
Keywords: | Human macrophage migration inhibitory factor (huMIF) inhibitor Tautomerase activity Nuclear factor kappa-B (NF-кB) Nitric oxide synthase Nitric oxide Inflammation |
本文献已被 ScienceDirect PubMed 等数据库收录! |
|