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

被引:30
作者
Alam, Athar [2 ]
Pal, Chinmay [2 ]
Goyal, Manish [2 ]
Kundu, Milan Kumar [3 ]
Kumar, Rahul [2 ]
Iqbal, Mohd Shameel [2 ]
Dey, Sumanta [2 ]
Bindu, Samik [2 ]
Sarkar, Souvik [2 ]
Pal, Uttam [4 ,5 ]
Maiti, Nakul C. [4 ,5 ]
Adhikari, Susanta [1 ]
Bandyopadhyay, Uday [2 ]
机构
[1] Univ Calcutta, Dept Chem, Kolkata 700009, W Bengal, India
[2] Indian Inst Chem Biol, Dept Infect Dis & Immunol, Kolkata 700032, W Bengal, India
[3] Univ Burdwan, Dept Chem, Burdwan 713104, W Bengal, India
[4] Indian Inst Chem Biol, Dept Biol Struct, Kolkata 700032, W Bengal, India
[5] Indian Inst Chem Biol, Bioinformat Div, Kolkata 700032, W Bengal, India
关键词
Human macrophage migration inhibitory factor (huMIF) inhibitor; Tautomerase activity; Nuclear factor kappa-B (NF-kappa B); Nitric oxide synthase; Nitric oxide; Inflammation; NF-KAPPA-B; MIF TAUTOMERASE ACTIVITY; PLASMODIUM-FALCIPARUM; NITRIC-OXIDE; ACTIVE-SITE; OXIDATIVE STRESS; REGULATORY ROLE; CELLS; IDENTIFICATION; LOCALIZATION;
D O I
10.1016/j.bmc.2011.10.056
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
070307 [化学生物学]; 071010 [生物化学与分子生物学];
摘要
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-kappa B 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. (C) 2011 Elsevier Ltd. All rights reserved.
引用
收藏
页码:7365 / 7373
页数:9
相关论文
共 46 条
[1]
ISO-1 binding to the tautomerase active site of MIF inhibits its pro-inflammatory activity and increases survival in severe sepsis [J].
Al-Abed, Y ;
Dabideen, D ;
Aljabari, B ;
Valster, A ;
Messmer, D ;
Ochani, M ;
Tanovic, M ;
Ochani, K ;
Bacher, M ;
Nicoletti, F ;
Metz, C ;
Pavlov, VA ;
Miller, EJ ;
Tracey, KJ .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2005, 280 (44) :36541-36544
[2]
Cysteine-3 and cysteine-4 are essential for the thioredoxin-like oxidoreductase and antioxidant activities of Plasmodium falciparum macrophage migration inhibitory factor [J].
Alam, Athar ;
Goyal, Manish ;
Iqbal, Mohd Shameel ;
Bindu, Samik ;
Dey, Sumanta ;
Pal, Chinmay ;
Maity, Pallab ;
Mascarenhas, Nahren Manuel ;
Ghoshal, Nanda ;
Bandyopadhyay, Uday .
FREE RADICAL BIOLOGY AND MEDICINE, 2011, 50 (11) :1659-1668
[3]
Migration inhibitory factor up-regulates vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 via Src, PI3 kinase, and NFκB [J].
Amin, MA ;
Haas, CS ;
Zhu, K ;
Mansfield, PJ ;
Kim, MJ ;
Lackowski, NP ;
Koch, AE .
BLOOD, 2006, 107 (06) :2252-2261
[4]
SPECIFICITY OF DOPACHROME TAUTOMERASE AND INHIBITION BY CARBOXYLATED INDOLES - CONSIDERATIONS ON THE ENZYME ACTIVE-SITE [J].
AROCA, P ;
SOLANO, F ;
GARCIABORRON, JC ;
LOZANO, JA .
BIOCHEMICAL JOURNAL, 1991, 277 :393-397
[5]
An essential regulatory role for macrophage migration inhibitory factor in T-cell activation [J].
Bacher, M ;
Metz, CN ;
Calandra, T ;
Mayer, K ;
Chesney, J ;
Lohoff, M ;
Gemsa, D ;
Donnelly, T ;
Bucala, R .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (15) :7849-7854
[6]
Synthesis and biological activity of novel MIF antagonists [J].
Balachandran, Sarala ;
Gadekar, Pradip K. ;
Parkale, Santosh ;
Yadav, Vitthal N. ;
Kamath, Divya ;
Ramaswamy, Sneha ;
Sharma, Somesh ;
Vishwakarma, Ram A. ;
Dagia, Nilesh M. .
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2011, 21 (05) :1508-1511
[7]
Novel derivatives of ISO-1 as potent inhibitors of MIF biological function [J].
Balachandran, Sarala ;
Rodge, Atish ;
Gadekar, Pradip K. ;
Yadav, Vitthal N. ;
Kamath, Divya ;
Chetrapal-Kunwar, Anshu ;
Bhatt, Pooja ;
Srinivasan, Shaila ;
Sharma, Somesh ;
Vishwakarma, Ram A. ;
Dagia, Nilesh M. .
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2009, 19 (16) :4773-4776
[8]
PURIFICATION, BIOACTIVITY, AND SECONDARY STRUCTURE-ANALYSIS OF MOUSE AND HUMAN MACROPHAGE-MIGRATION INHIBITORY FACTOR (MIF) [J].
BERNHAGEN, J ;
MITCHELL, RA ;
CALANDRA, T ;
VOELTER, W ;
CERAMI, A ;
BUCALA, R .
BIOCHEMISTRY, 1994, 33 (47) :14144-14155
[9]
The emerging role of MIF in septic shock and infection [J].
Bernhagen, J ;
Calandra, T ;
Bucala, R .
BIOTHERAPY, 1995, 8 (02) :123-127
[10]
MECHANISM OF A REACTION IN VITRO ASSOCIATED WITH DELAYED-TYPE HYPERSENSITIVITY [J].
BLOOM, BR ;
BENNETT, B .
SCIENCE, 1966, 153 (3731) :80-&