title: Anti-inflammatory thiazine alkaloids isolated from the New Zealand ascidian Aplidium sp.: inhibitors of the neutrophil respiratory burst in a model of gouty arthritis.
abstract: Ascidiathiazones A (3) and B (4), two new tricyclic thiazine-containing quinolinequinone alkaloids, were isolated from the New Zealand ascidian Aplidium species. Both compounds inhibited the in vitro production of superoxide by PMA-stimulated human neutrophils in a dose-dependent manner with IC50 1.55 +/- 0.32 and 0.44 +/- 0.09 microM, respectively. In vivo inhibition of superoxide production by peritoneal neutrophils in a murine model of gout was observed for both compounds with oral doses of 25.6 micromol/kg. Ascidiathiazone A (3) was synthesized in four steps from 8-hydroxyquinoline-2-carboxylic acid.
authors.affiliation: TerraMarine Pharmaceuticals, Department of Chemistry, The University of Auckland, Private Bag 92019, Auckland, New Zealand.
authors.forename: A Norrie
authors.initials: AN
authors.lastname: Pearce
authors.forename: Elizabeth W
authors.initials: EW
authors.lastname: Chia
authors.forename: Michael V
authors.initials: MV
authors.lastname: Berridge
authors.forename: George R
authors.initials: GR
authors.lastname: Clark
authors.forename: Jacquie L
authors.initials: JL
authors.lastname: Harper
authors.forename: Lesley
authors.initials: L
authors.lastname: Larsen
authors.forename: Elizabeth W
authors.initials: EW
authors.lastname: Maas
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Page
authors.forename: Nigel B
authors.initials: NB
authors.lastname: Perry
authors.forename: Victoria L
authors.initials: VL
authors.lastname: Webb
authors.forename: Brent R
authors.initials: BR
authors.lastname: Copp
mesh_terms: D000470:Alkaloids / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D015210:Arthritis, Gouty / Q000139:chemically induced; D004305:Dose-Response Relationship, Drug; D006801:Humans; D051379:Mice; D008954:Models, Biological; D009504:Neutrophils / Q000187:drug effects*; D009520:New Zealand; D016897:Respiratory Burst / Q000187:drug effects; D013481:Superoxides / Q000097:blood; D013843:Thiazines / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D014561:Urochordata / Q000737:chemistry*
chemical_list: D000470:Alkaloids; D000894:Anti-Inflammatory Agents, Non-Steroidal; D013843:Thiazines; C521537:ascidiathiazone A; C521538:ascidiathiazone B; D013481:Superoxides