Structural-activity relationship study of highly-functionalized imidazolines as potent inhibitors of nuclear transcription factor-kappaB mediated IL-6 production.
We herein describe the synthesis and anti-inflammatory properties of a small library of imidazoline-based NF-kappaB inhibitors. The structure-activity relationship of various substituents on an imidazoline core structure was evaluated for the ability to inhibit NF-kappaB mediated IL-6 production. Optimization of the scaffolds was pursued by correlating luciferase-based NF-kappaB reporter assays with inhibition of IL-6 production in IL-1beta stimulated human blood. Several derivatives were found to inhibit NF-kappaB mediated IL-6 production in the nanomolar range in IL-1beta stimulated human blood.
Kahlon
Daljinder K
DK
Department of Chemistry, Michigan State University, East Lansing, MI 48824, USA.
Lansdell
Theresa A
TA
Fisk
Jason S
JS
Tepe
Jetze J
JJ