Abstract
A series of novel 1,2,4-oxadiazole, phthalimide, amide and other derivatives of ISO-1 were synthesized and probed for inhibition of macrophage migration inhibitory factor (MIF) activity. Several compounds inhibited MIF enzymatic activity at levels better than ISO-1. Of note, compounds 7, 22, 23, 24, 25 and 27 inhibited the spontaneous secretion/release/recognition of MIF from freshly isolated human peripheral blood mononuclear cells and, more importantly, inhibited the MIF-induced production of interleukin-6 (IL-6) and/or interleukin-1beta (IL-1beta) significantly better than ISO-1.
MeSH terms
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Amides / chemistry
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Anti-Inflammatory Agents / chemical synthesis*
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Anti-Inflammatory Agents / chemistry
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Anti-Inflammatory Agents / pharmacology
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Cell Line
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Humans
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Interleukin-1beta / metabolism
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Interleukin-6 / metabolism
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Isoxazoles / chemical synthesis
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Isoxazoles / chemistry*
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Isoxazoles / pharmacology
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Oxadiazoles / chemistry
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Phthalimides / chemistry
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Receptors, Immunologic / antagonists & inhibitors*
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Receptors, Immunologic / metabolism
Substances
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3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazoleacetic acid methyl ester
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Amides
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Anti-Inflammatory Agents
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Interleukin-1beta
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Interleukin-6
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Isoxazoles
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Oxadiazoles
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Phthalimides
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Receptors, Immunologic
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macrophage migration inhibitory factor receptor
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phthalimide