A novel dicyanotriterpenoid, 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-onitrile, active at picomolar concentrations for inhibition of nitric oxide production

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 inhibi...

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Veröffentlicht in:	Bioorganic & medicinal chemistry letters 2002-04, Vol.12 (7), p.1027-1030
Hauptverfasser:	HONDA, Tadashi, HONDA, Yukiko, FAVALORO, Frank G, GRIBBLE, Gordon W, SUH, Nanjoo, PLACE, Andrew E, RENDI, Mara H, SPORN, Michael B
Format:	Artikel
Sprache:	eng
Schlagworte:	Animals Biological and medical sciences Bones, joints and connective tissue. Antiinflammatory agents Dexamethasone - pharmacology Interferon-gamma - pharmacology Macrophages - drug effects Macrophages - metabolism Medical sciences Mice Molecular Structure Nitric Oxide - antagonists & inhibitors Nitric Oxide - biosynthesis Nitriles - chemical synthesis Nitriles - chemistry Nitriles - pharmacology Oleanolic Acid - analogs & derivatives Oleanolic Acid - chemical synthesis Oleanolic Acid - chemistry Oleanolic Acid - pharmacology Pharmacology. Drug treatments Structure-Activity Relationship Triterpenes - chemical synthesis Triterpenes - chemistry Triterpenes - pharmacology
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Zusammenfassung:	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.
ISSN:	0960-894X
DOI:	10.1016/s0960-894x(02)00105-1