Anti-inflammatory thiazine alkaloids isolated from the New Zealand ascidian Aplidium sp.: inhibitors of the neutrophil respiratory burst in a model of gouty arthritis.
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.
Pearce
A Norrie
AN
TerraMarine Pharmaceuticals, Department of Chemistry, The University of Auckland, Private Bag 92019, Auckland, New Zealand.
Chia
Elizabeth W
EW
Berridge
Michael V
MV
Clark
George R
GR
Harper
Jacquie L
JL
Larsen
Lesley
L
Maas
Elizabeth W
EW
Page
Michael J
MJ
Perry
Nigel B
NB
Webb
Victoria L
VL
Copp
Brent R
BR
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*
D000470:Alkaloids; D000894:Anti-Inflammatory Agents, Non-Steroidal; D013843:Thiazines; C521537:ascidiathiazone A; C521538:ascidiathiazone B; D013481:Superoxides