Abstract
Sixteen new thiazine-quinoline-quinones have been synthesised, plus one bicyclic analogue. These compounds inhibited neutrophil superoxide production in vitro with IC(50)s as low 60 nM. Compounds with high in vitro anti-inflammatory activity were also tested in a mouse model of acute inflammation. The most active compounds inhibited both neutrophil infiltration and superoxide production at doses 2.5 micromol/kg, highlighting their potential for development as novel NSAIDs.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Anti-Inflammatory Agents, Non-Steroidal / chemical synthesis*
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Anti-Inflammatory Agents, Non-Steroidal / chemistry
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Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
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Arthritis, Gouty / drug therapy*
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Arthritis, Gouty / metabolism
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Cell Proliferation / drug effects
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Disease Models, Animal*
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HL-60 Cells
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Humans
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Inflammation / drug therapy*
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Inflammation / metabolism
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Male
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Mice
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Mice, Inbred C57BL
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Neutrophils / drug effects*
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Quinolines / chemistry
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Quinones / chemistry
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Respiratory Burst / drug effects*
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Structure-Activity Relationship
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Superoxides / metabolism
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Thiazines / chemistry
Substances
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Anti-Inflammatory Agents, Non-Steroidal
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Quinolines
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Quinones
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Thiazines
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Superoxides
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quinoline