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

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 (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. ISSN 0968-0896

Full text not available from this repository.

Official URL: http://www.sciencedirect.com/science/article/pii/S...

Related URL: http://dx.doi.org/10.1016/j.bmc.2011.10.056

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.

Item Type:Article
Source:Copyright of this article belongs to Elsevier Science.
Keywords:Human Macrophage Migration Inhibitory Factor (huMIF) Inhibitor; Tautomerase Activity; Nuclear Factor Kappa-B (NF-κB); Nitric Oxide Synthase; Nitric Oxide; Inflammation
ID Code:99571
Deposited On:24 Nov 2016 10:54
Last Modified:24 Nov 2016 10:54

Repository Staff Only: item control page