Nuclear factor-kappaB mediated inhibition of cytokine production by imidazoline scaffolds.
The mammalian nuclear transcription factor NF-kappaB is responsible for the transcription of multiple cytokines, including the pro-inflammatory cytokines tumor necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6). Elevated levels of pro-inflammatory cytokines play an important role in the pathogenesis of inflammatory disorders such as rheumatoid arthritis (RA). Inhibition of the pro-inflammatory transcription factor NF-kappaB has therefore been identified as a possible therapeutic treatment for RA. We describe herein the synthesis and biological activity of a series of imidazoline-based scaffolds as potent inhibitors of NF-kappaB mediated gene transcription in cell culture as well as inhibitors of TNF-alpha and IL-6 production in interleukin 1 beta (IL-1beta) stimulated human blood.
Kahlon
Daljinder K
DK
Department of Chemistry, Michigan State University, East Lansing, Michigan 48824, USA.
Lansdell
Theresa A
TA
Fisk
Jason S
JS
Hupp
Christopher D
CD
Friebe
Timothy L
TL
Hovde
Stacy
S
Jones
A Daniel
AD
Dyer
Richard D
RD
Henry
R William
RW
Tepe
Jetze J
JJ
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D048288:Imidazolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D066298:In Vitro Techniques; D053583:Interleukin-1beta / Q000494:pharmacology; D015850:Interleukin-6 / Q000096:biosynthesis; D016328:NF-kappa B / Q000235:genetics / Q000502:physiology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014158:Transcription, Genetic / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D000093242:Interleukin-6 Inhibitors
D000894:Anti-Inflammatory Agents, Non-Steroidal; D048288:Imidazolines; D053583:Interleukin-1beta; D015850:Interleukin-6; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D000093242:Interleukin-6 Inhibitors