Synthesis and anti-inflammatory structure-activity relationships of thiazine-quinoline-quinones: inhibitors of the neutrophil respiratory burst in a model of acute gouty arthritis.
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.
Malaghan Institute of Medical Research, PO Box 7060, Wellington South, New Zealand.
Elizabeth W
EW
Chia
A Norrie
AN
Pearce
Michael V
MV
Berridge
Lesley
L
Larsen
Nigel B
NB
Perry
Catherine E
CE
Sansom
Colette A
CA
Godfrey
Lyall R
LR
Hanton
Guo-Liang Leon
GL
Lu
Michaela
M
Walton
William A
WA
Denny
Victoria L
VL
Webb
Brent R
BR
Copp
Jacquie L
JL
Harper
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015210:Arthritis, Gouty / Q000188:drug therapy* / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D018922:HL-60 Cells; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000187:drug effects*; D011804:Quinolines / Q000737:chemistry; D011809:Quinones / Q000737:chemistry; D016897:Respiratory Burst / Q000187:drug effects*; D013329:Structure-Activity Relationship; D013481:Superoxides / Q000378:metabolism; D013843:Thiazines / Q000737:chemistry
D000894:Anti-Inflammatory Agents, Non-Steroidal; D011804:Quinolines; D011809:Quinones; D013843:Thiazines; D013481:Superoxides; C037219:quinoline