Abstract
In order to develop new inhibitors of NF-kappaB activation, we designed and synthesized dehydroxymethyl derivatives of epoxyquinomicin C, namely, DHM2EQ and its regioisomer DHM3EQ. These derivatives were synthesized from 2,5-dimethoxyaniline in 5 steps. Since DHM2EQ was more active and less toxic than DHM3EQ, its stereochemical configuration was determined by X-ray crystallographic analysis. Each enantiomer of the protected DHM2EQ was separated by a chiral column and deprotected. DHM2EQ inhibited TNF-alpha-induced activation of NF-kappaB in human T cell leukemia cells, and also inhibited collagen-induced arthritis in a rheumatoid model in mice.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antineoplastic Agents / chemical synthesis
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Antineoplastic Agents / chemistry*
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Antineoplastic Agents / pharmacology
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Antirheumatic Agents / chemical synthesis
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Antirheumatic Agents / pharmacology
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Arthritis, Rheumatoid / chemically induced
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Arthritis, Rheumatoid / prevention & control
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Benzamides / chemical synthesis
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Benzamides / chemistry*
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Benzamides / pharmacology
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Biotransformation / drug effects
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Circular Dichroism
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Humans
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Jurkat Cells
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Magnetic Resonance Spectroscopy
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Mice
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NF-kappa B / antagonists & inhibitors*
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Oxidation-Reduction
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Quinones / chemical synthesis
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Quinones / chemistry*
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Quinones / pharmacology
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Stereoisomerism
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Structure-Activity Relationship
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Tumor Necrosis Factor-alpha / metabolism
Substances
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Antineoplastic Agents
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Antirheumatic Agents
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Benzamides
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NF-kappa B
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Quinones
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Tumor Necrosis Factor-alpha
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epoxyquinomicin C