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: A Norrie Pearce, Elizabeth W Chia, Michael V Berridge, George R Clark, Jacquie L Harper, Lesley Larsen, Elizabeth W Maas, Michael J Page, Nigel B Perry, Victoria L Webb, Brent R Copp
• Journal: Journal of natural products (J Nat Prod) Vol. 70 Issue 6 Pg. 936-40 (Jun 2007) ISSN: 0163-3864 [Print] United States
• PMID: 17497807 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

• Alkaloids (chemistry, isolation & purification, pharmacology)
• Animals
• Anti-Inflammatory Agents, Non-Steroidal (chemistry, isolation & purification, 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, isolation & purification, pharmacology)
• Urochordata (chemistry)