Synthesis of chroman-2-carboxylic acid N-(substituted)phenylamides and their inhibitory effect on nuclear factor-kappaB (NF-kappaB) activation

A series of chroman-2-carboxylic acid N-(substituted)phenylamides (2a-s, 3a-j) were synthesized. Their ability to inhibit nuclear factor-kappaB (NF-kappaB) activity was evaluated in lipopolysaccharide (LPS)-stimulated macrophage RAW 264.7 cells and their antioxidant activity was examined. NF-kappaB...

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Bibliographic Details
Published in:Archives of pharmacal research 2008-02, Vol.31 (2), p.133-141
Main Authors: Kwak, Jae-Hwan, Won, Sun-Woo, Kim, Tae-Jeong, Roh, Eunmiri, Kang, Han-Young, Lee, Hyo Won, Jung, Jae-Kyung, Hwang, Bang Yeon, Kim, Youngsoo, Cho, Jungsook, Lee, Heesoon
Format: Article
Language:English
Subjects:
Animals
Antioxidants - pharmacology
Biphenyl Compounds
Brain Chemistry - drug effects
Cell Line
Chromans - chemical synthesis
Chromans - pharmacology
Free Radical Scavengers - pharmacology
Indicators and Reagents
Lipid Peroxidation - drug effects
Lipopolysaccharides - pharmacology
Macrophages - drug effects
Magnetic Resonance Spectroscopy
Mice
NF-kappa B - antagonists & inhibitors
NF-kappa B - biosynthesis
NF-kappa B - genetics
Picrates - pharmacology
Rats
Structure-Activity Relationship
Transcription, Genetic
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Summary:A series of chroman-2-carboxylic acid N-(substituted)phenylamides (2a-s, 3a-j) were synthesized. Their ability to inhibit nuclear factor-kappaB (NF-kappaB) activity was evaluated in lipopolysaccharide (LPS)-stimulated macrophage RAW 264.7 cells and their antioxidant activity was examined. NF-kappaB inhibition by chroman compounds was not related to their antioxidant activity. Compounds with -H, -NO2 monosubstituents and -OCH3, -CF3 disubstituents on the phenyl ring were poor inhibitors of NF-kB activity. Compounds with -CH3, -CF3, -CI monosubstituents or -CI, -CH3 disubstituents exhibited moderate to good NF-kappaB activity inhibition (IC50: 18.2-95.8 microM). The most active NF-kappaB inhibitor, 2s, contained a 4-CI (IC50: 18.2 microM) substituent on the phenyl ring and was slightly more potent than the compound KL-1156 (1) (IC50: 43.9 microM).
ISSN:0253-6269