Anti-inflammatory thiazine alkaloids isolated from the New Zealand ascidian Aplidium sp.: inhibitors of the neutrophil respiratory burst in a model of gouty arthritis

J Nat Prod. 2007 Jun;70(6):936-40. doi: 10.1021/np060626o. Epub 2007 May 11.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaloids / chemistry
  • Alkaloids / isolation & purification
  • Alkaloids / pharmacology*
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / chemistry
  • Anti-Inflammatory Agents, Non-Steroidal / isolation & purification
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Arthritis, Gouty / chemically induced
  • Dose-Response Relationship, Drug
  • Humans
  • Mice
  • Models, Biological*
  • Neutrophils / drug effects*
  • New Zealand
  • Respiratory Burst / drug effects
  • Superoxides / blood
  • Thiazines / chemistry
  • Thiazines / isolation & purification
  • Thiazines / pharmacology*
  • Urochordata / chemistry*

Substances

  • Alkaloids
  • Anti-Inflammatory Agents, Non-Steroidal
  • Thiazines
  • ascidiathiazone A
  • ascidiathiazone B
  • Superoxides