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
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Research Support, Non-U.S. Gov't
MeSH terms
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Alkaloids / chemistry
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Alkaloids / isolation & purification
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Alkaloids / pharmacology*
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Animals
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Anti-Inflammatory Agents, Non-Steroidal / chemistry
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Anti-Inflammatory Agents, Non-Steroidal / isolation & purification
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Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
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Arthritis, Gouty / chemically induced
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Dose-Response Relationship, Drug
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Humans
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Mice
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Models, Biological*
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Neutrophils / drug effects*
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New Zealand
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Respiratory Burst / drug effects
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Superoxides / blood
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Thiazines / chemistry
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Thiazines / isolation & purification
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Thiazines / pharmacology*
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Urochordata / chemistry*
Substances
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Alkaloids
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Anti-Inflammatory Agents, Non-Steroidal
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Thiazines
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ascidiathiazone A
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ascidiathiazone B
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Superoxides