Studies on the reactivity of CDDO, a promising new chemopreventive and chemotherapeutic agent: implications for a molecular mechanism of action

Robin D Couch; R Greg Browning; Tadashi Honda; Gordon W Gribble; Dennis L Wright; Michael B Sporn; Amy C Anderson

doi:10.1016/j.bmcl.2005.03.031

Studies on the reactivity of CDDO, a promising new chemopreventive and chemotherapeutic agent: implications for a molecular mechanism of action

Bioorg Med Chem Lett. 2005 May 2;15(9):2215-9. doi: 10.1016/j.bmcl.2005.03.031.

Authors

Robin D Couch¹, R Greg Browning, Tadashi Honda, Gordon W Gribble, Dennis L Wright, Michael B Sporn, Amy C Anderson

Affiliation

¹ Department of Chemistry, Dartmouth College, Hanover, NH 03755, USA.

PMID: 15837296
DOI: 10.1016/j.bmcl.2005.03.031

Abstract

CDDO, a semi-synthetic triterpenoid derived from oleanolic acid, has the potential to be used as a chemopreventive and chemotherapeutic agent. The structure of CDDO contains two alpha,beta-unsaturated carbonyl moieties, suggesting a mechanism of action involving a conjugate nucleophilic addition. Spectroscopic evaluation with thiol nucleophiles illustrates that an addition does indeed occur, but this addition is selective and reversible.

Publication types

Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, P.H.S.

MeSH terms

Dithiothreitol
Kinetics
Molecular Conformation
Molecular Structure
Nitric Oxide / antagonists & inhibitors
Oleanolic Acid / analogs & derivatives*
Oleanolic Acid / chemical synthesis
Oleanolic Acid / pharmacology
Spectrophotometry, Ultraviolet

Substances

2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid
Nitric Oxide
Oleanolic Acid
Dithiothreitol

Grants and funding

CA78814/CA/NCI NIH HHS/United States