A Novel Dicyanotriterpenoid, 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-onitrile, Active at Picomolar Concentrations for Inhibition of Nitric Oxide Production

Bioorg Med Chem Lett. 2002 Apr 8;12(7):1027-30. doi: 10.1016/s0960-894x(02)00105-1.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Dexamethasone / pharmacology
  • Interferon-gamma / pharmacology
  • Macrophages / drug effects*
  • Macrophages / metabolism
  • 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
  • Structure-Activity Relationship
  • Triterpenes / chemical synthesis*
  • Triterpenes / chemistry
  • Triterpenes / pharmacology*

Substances

  • Nitriles
  • Triterpenes
  • Nitric Oxide
  • cyanogen
  • Oleanolic Acid
  • Dexamethasone
  • Interferon-gamma