title: A novel dicyanotriterpenoid, 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-onitrile, active at picomolar concentrations for inhibition of nitric oxide production.
abstract: New oleanane triterpenoids with various substituents at the C-17 position of 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid (CDDO) and methyl 2-carboxy-3,12-dioxooleana-1,9(11)-dien-28-oate were synthesized. Among them, 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-onitrile shows extremely high inhibitory activity (IC(50)=1 pM level) against production of nitric oxide induced by interferon-gamma in mouse macrophages. This potency is about 100 times and 30 times more potent than CDDO and dexamethasone, respectively.
authors.affiliation: Department of Chemistry, Dartmouth College, Hanover, NH 03755, USA.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Honda
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Honda
authors.forename: Frank G
authors.initials: FG
authors.lastname: Favaloro
authors.forename: Gordon W
authors.initials: GW
authors.lastname: Gribble
authors.forename: Nanjoo
authors.initials: N
authors.lastname: Suh
authors.forename: Andrew E
authors.initials: AE
authors.lastname: Place
authors.forename: Mara H
authors.initials: MH
authors.lastname: Rendi
authors.forename: Michael B
authors.initials: MB
authors.lastname: Sporn
mesh_terms: D000818:Animals; D003907:Dexamethasone / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D015394:Molecular Structure; D009569:Nitric Oxide / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D009570:Nitriles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D009828:Oleanolic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014315:Triterpenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D009570:Nitriles; D014315:Triterpenes; D009569:Nitric Oxide; C011206:cyanogen; D009828:Oleanolic Acid; D003907:Dexamethasone; D007371:Interferon-gamma