title: Inhibition of cytokine production by hymenialdisine derivatives.
abstract: We describe herein the synthesis and biological activity of two indoloazepines that are structurally related to the marine sponge metabolite hymenialdisine. The natural product hymenialdisine was found to be a potent inhibitor of interleukin-2 (IC(50) = 2.4 microM) and tumor necrosis factor alpha (IC(50) = 1.4 microM) production. One of the hymenialdisine derived indoloazepines was found to also inhibit interleukin-2 (IC(50) = 3.5 microM) and tumor necrosis factor alpha (IC(50) = 8.2 microM) production.
authors.affiliation: Department of Chemistry, Michigan State University, East Lansing, MI 48824, USA.
authors.forename: Vasudha
authors.initials: V
authors.lastname: Sharma
authors.forename: Theresa A
authors.initials: TA
authors.lastname: Lansdell
authors.forename: Guangyi
authors.initials: G
authors.lastname: Jin
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; D001381:Azepines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D018360:Crystallography, X-Ray; D016207:Cytokines / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D007376:Interleukin-2 / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D015394:Molecular Structure; D011758:Pyrroles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000096:biosynthesis
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D001381:Azepines; D016207:Cytokines; D007211:Indoles; D007376:Interleukin-2; D011758:Pyrroles; D014409:Tumor Necrosis Factor-alpha; C107079:hymenialdisine