Structural-activity relationship study of highly-functionalized imidazolines as potent inhibitors of nuclear transcription factor-kappaB mediated IL-6 production

Daljinder K Kahlon; Theresa A Lansdell; Jason S Fisk; Jetze J Tepe

doi:10.1016/j.bmc.2009.03.002

Structural-activity relationship study of highly-functionalized imidazolines as potent inhibitors of nuclear transcription factor-kappaB mediated IL-6 production

Bioorg Med Chem. 2009 Apr 15;17(8):3093-103. doi: 10.1016/j.bmc.2009.03.002. Epub 2009 Mar 9.

Authors

Daljinder K Kahlon¹, Theresa A Lansdell, Jason S Fisk, Jetze J Tepe

Affiliation

¹ Department of Chemistry, Michigan State University, East Lansing, MI 48824, USA.

PMID: 19328000
DOI: 10.1016/j.bmc.2009.03.002

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cells, Cultured
HeLa Cells
Humans
Imidazolines / chemistry*
Imidazolines / pharmacology*
Interleukin-1beta / blood
Interleukin-1beta / pharmacology
Interleukin-6 / biosynthesis*
Interleukin-6 / blood
NF-kappa B / antagonists & inhibitors*
NF-kappa B / genetics
NF-kappa B / metabolism
Peptide Fragments / blood
Peptide Fragments / pharmacology
Structure-Activity Relationship
Transcriptional Activation / drug effects

Substances

Imidazolines
Interleukin-1beta
Interleukin-6
NF-kappa B
Peptide Fragments
interleukin-1beta (163-171)