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 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).
Kwak
Jae-Hwan
JH
College of Pharmacy, Chungbuk National University, Cheongju 361-763, Korea.
Won
Sun-Woo
SW
Kim
Tae-Jeong
TJ
Roh
Eunmiri
E
Kang
Han-Young
HY
Lee
Hyo Won
HW
Jung
Jae-Kyung
JK
Hwang
Bang Yeon
BY
Kim
Youngsoo
Y
Cho
Jungsook
J
Lee
Heesoon
H
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001713:Biphenyl Compounds; D001923:Brain Chemistry / Q000187:drug effects; D002460:Cell Line; D002839:Chromans / Q000138:chemical synthesis* / Q000494:pharmacology*; D016166:Free Radical Scavengers / Q000494:pharmacology; D007202:Indicators and Reagents; D015227:Lipid Peroxidation / Q000187:drug effects; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics; D010851:Picrates / Q000494:pharmacology; D051381:Rats; D013329:Structure-Activity Relationship; D014158:Transcription, Genetic
D000975:Antioxidants; D001713:Biphenyl Compounds; D002839:Chromans; D016166:Free Radical Scavengers; D007202:Indicators and Reagents; D008070:Lipopolysaccharides; D016328:NF-kappa B; D010851:Picrates; C004931:1,1-diphenyl-2-picrylhydrazyl