New synthetic triterpenoids: potent agents for prevention and treatment of tissue injury caused by inflammatory and oxidative stress

J Nat Prod. 2011 Mar 25;74(3):537-45. doi: 10.1021/np100826q. Epub 2011 Feb 10.

Abstract

We review the original rationale for the development and the chemistry of a series of new synthetic oleanane triterpenoids (SO), based on oleanolic acid (1) as a starting material. Many of the new compounds that have been made, such as 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid ("CDDO", 8), are highly potent (activities found at levels below 1 nM) anti-inflammatory agents, as measured by their ability to block the cellular synthesis of the enzyme inducible nitric oxide synthase (iNOS) in activated macrophages. Details of the organic synthesis of new SO and their chemical mechanisms of biological activity are reviewed, as is formation of biotin conjugates for investigation of protein targets. Finally, we give a brief summary of important biological activities of SO in many organ systems in numerous animal models. Clinical investigation of a new SO (methyl 2-cyano-3,12-dioxooleana-1,9(11)dien-28-oate, "CDDO-Me", bardoxolone methyl, 13) is currently in progress.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Anti-Inflammatory Agents* / chemical synthesis
  • Anti-Inflammatory Agents* / chemistry
  • Anti-Inflammatory Agents* / pharmacology
  • Models, Animal
  • Molecular Structure
  • Nitric Oxide Synthase Type II / antagonists & inhibitors
  • Oleanolic Acid* / chemical synthesis
  • Oleanolic Acid* / chemistry
  • Oleanolic Acid* / pharmacology
  • Oxidative Stress / physiology*
  • Soft Tissue Injuries / drug therapy*

Substances

  • Anti-Inflammatory Agents
  • Oleanolic Acid
  • Nitric Oxide Synthase Type II