title: 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).
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.
authors.affiliation: Department of Chemistry, Dartmouth College, Hanover, NH 03755, USA.
authors.forename: Evans O
authors.initials: EO
authors.lastname: Onyango
authors.affiliation: Department of Chemistry, Dartmouth College, Hanover, NH 03755, USA.
authors.forename: Liangfeng
authors.initials: L
authors.lastname: Fu
authors.affiliation: Department of Pharmacology and Toxicology, Dartmouth Medical School, Hanover, NH 03755, USA.
authors.forename: Martine
authors.initials: M
authors.lastname: Cao
authors.affiliation: Department of Pharmacology and Toxicology, Dartmouth Medical School, Hanover, NH 03755, USA.
authors.forename: Karen T
authors.initials: KT
authors.lastname: Liby
authors.affiliation: Department of Pharmacology and Toxicology, Dartmouth Medical School, Hanover, NH 03755, USA.
authors.forename: Michael B
authors.initials: MB
authors.lastname: Sporn
authors.affiliation: Department of Chemistry, Dartmouth College, Hanover, NH 03755, USA. Electronic address: ggribble@dartmouth.edu.
authors.forename: Gordon W
authors.initials: GW
authors.lastname: Gribble
mesh_terms: D000596:Amino Acids / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical / Q000379:methods; D006801:Humans; D051379:Mice; D009569:Nitric Oxide / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D009828:Oleanolic Acid / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000596:Amino Acids; D009569:Nitric Oxide; D009828:Oleanolic Acid; C445068:bardoxolone methyl
keywords: Amino acid conjugate; Antiinflammatory; Bardoxolone; CDDO; HO-1 expression; Nitric oxide; Pancreatic cancer; Triterpenoid