Synthesis and biological evaluation of amino acid methyl ester conjugates of 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid against the production of nitric oxide (NO)

Bioorg Med Chem Lett. 2014 Jan 15;24(2):532-4. doi: 10.1016/j.bmcl.2013.12.034. Epub 2013 Dec 15.

Abstract

2-Cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid (CDDO, 2) was condensed with various amino acid methyl esters at the C-28 carboxylic acid. The new amide conjugates were evaluated for their inhibition of nitric oxide (NO) production in RAW264.7 cells stimulated with interferon-γ (IFNγ). Of these new compounds, CDDO conjugates with alanine, valine, and serine are nearly equipotent to CDDO-ethyl amide (4), a triterpenoid with promising biological activity in numerous disease models. Some of these conjugates also induce the in vitro expression of heme oxygenase-1, and inhibit the proliferation of Panc-1343 pancreatic cells.

Keywords: Amino acid conjugate; Antiinflammatory; Bardoxolone; CDDO; HO-1 expression; Nitric oxide; Pancreatic cancer; Triterpenoid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids / chemistry
  • Amino Acids / pharmacology
  • Animals
  • Cell Line, Tumor
  • Dose-Response Relationship, Drug
  • Drug Evaluation, Preclinical / methods
  • Humans
  • Mice
  • Nitric Oxide / antagonists & inhibitors*
  • Nitric Oxide / biosynthesis*
  • Oleanolic Acid / analogs & derivatives*
  • Oleanolic Acid / chemistry
  • Oleanolic Acid / pharmacology

Substances

  • Amino Acids
  • Nitric Oxide
  • Oleanolic Acid
  • bardoxolone methyl