title: Nuclear factor-kappaB mediated inhibition of cytokine production by imidazoline scaffolds.
abstract: 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.
authors.affiliation: Department of Chemistry, Michigan State University, East Lansing, Michigan 48824, USA.
authors.forename: Daljinder K
authors.initials: DK
authors.lastname: Kahlon
authors.forename: Theresa A
authors.initials: TA
authors.lastname: Lansdell
authors.forename: Jason S
authors.initials: JS
authors.lastname: Fisk
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Hupp
authors.forename: Timothy L
authors.initials: TL
authors.lastname: Friebe
authors.forename: Stacy
authors.initials: S
authors.lastname: Hovde
authors.forename: A Daniel
authors.initials: AD
authors.lastname: Jones
authors.forename: Richard D
authors.initials: RD
authors.lastname: Dyer
authors.forename: R William
authors.initials: RW
authors.lastname: Henry
authors.forename: Jetze J
authors.initials: JJ
authors.lastname: Tepe
mesh_terms: 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
chemical_list: 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