Abstract
A series of novel (E)-1,3-diphenyl-1H-pyrazole derivatives containing O-benzyl oxime moiety were firstly synthesized and their immunosuppressive activities were evaluated. Among all the compounds, 4n exhibited the most potent inhibitory activity (IC50 = 1.18 μM for lymph node cells and IC50 = 0.28 μM for PI3Kγ), which was comparable to that of positive control. Moreover, selected compounds were tested for their inhibitory activities against IL-6 released in ConA-simulated mouse lymph node cells, 4n exhibited the most potent inhibitory ability. Furthermore, in order to study the preliminary mechanism of the compounds with potent inhibitory activity, the RT-PCR experiment was performed to assay the effect of selected compounds on mRNA expression of IL-6. Among them, compound 4n strongly inhibited the expression of IL-6 mRNA.
Keywords:
Immunosuppressant; Molecular docking; Oxime ethers; PI3Kγ; Pyrazole.
Copyright © 2015 Elsevier Masson SAS. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Class Ib Phosphatidylinositol 3-Kinase / metabolism
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Drug Design*
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Gene Expression Regulation / drug effects
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Immunosuppressive Agents / chemical synthesis
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Immunosuppressive Agents / chemistry
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Immunosuppressive Agents / pharmacology*
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Interleukin-6 / genetics
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Interleukin-6 / metabolism
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Lymph Nodes / cytology
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Lymph Nodes / drug effects
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Lymph Nodes / immunology
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Lymph Nodes / metabolism
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Mice
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Molecular Docking Simulation*
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Molecular Structure
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Oximes / chemistry
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Oximes / pharmacology*
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Phosphoinositide-3 Kinase Inhibitors
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Protein Kinase Inhibitors / chemical synthesis
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Protein Kinase Inhibitors / chemistry
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Protein Kinase Inhibitors / pharmacology*
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Pyrazoles / chemical synthesis
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Pyrazoles / chemistry
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Pyrazoles / pharmacology*
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Structure-Activity Relationship
Substances
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(E)-1,3-diphenyl-1H-pyrazole
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Immunosuppressive Agents
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Interleukin-6
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Oximes
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Phosphoinositide-3 Kinase Inhibitors
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Protein Kinase Inhibitors
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Pyrazoles
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RNA, Messenger
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Class Ib Phosphatidylinositol 3-Kinase
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Pik3cg protein, mouse