Synthesis and pharmacological evaluation of 2'-hydroxychalcones and flavones as inhibitors of inflammatory mediators generation.
2'-Hydroxy-3,4-dimethoxy-3',4'-dimethylchalcone (3a), 2'-hydroxy-3',4',3,4-tetramethoxychalcone (3b), and their corresponding flavones, 3',4'-dimethoxy-7,8-dimethylflavone (4a) and 3',4',7,8-tetramethoxyflavone (4b), were prepared from 3,4-dimethoxycinnamic acid and the respective phenol. The four compounds inhibited enzymic lipid peroxidation and showed weak peroxyl scavenging activity. They also reduced LTB4 release from human neutrophils stimulated by A23187. The chalcone 3b was the only compound able to inhibit in a concentration-dependent way, synovial human recombinant phospholipase A2 activity, human platelet TXB2 generation, and human neutrophil degranulation. This chalcone exerted topical antiinflammatory effects in mice.
Ballesteros
J F
JF
Departamento de Farmacología, Universidad de Valencia, Facultad de Farmacia, Burjassot, Spain.
Sanz
M J
MJ
Ubeda
A
A
Miranda
M A
MA
Iborra
S
S
Payá
M
M
Alcaraz
M J
MJ
D000818:Animals; D015550:Cell Degranulation / Q000187:drug effects; D002599:Chalcone / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D047188:Chalcones; D015777:Eicosanoids / Q000096:biosynthesis; D005419:Flavonoids / Q000138:chemical synthesis* / Q000494:pharmacology; D016166:Free Radical Scavengers; D006801:Humans; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors*; D015227:Lipid Peroxidation / Q000187:drug effects; D051379:Mice; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D010196:Pancreatic Elastase / Q000378:metabolism; D010741:Phospholipases A / Q000037:antagonists & inhibitors; D054467:Phospholipases A2; D013582:Synovial Fluid / Q000201:enzymology
D047188:Chalcones; D015777:Eicosanoids; D005419:Flavonoids; D016166:Free Radical Scavengers; D018836:Inflammation Mediators; D002599:Chalcone; D010741:Phospholipases A; D054467:Phospholipases A2; D010196:Pancreatic Elastase; C013031:2'-hydroxychalcone