Evaluation of labdane derivatives as potential anti-inflammatory agents.
In the present study, a series of labdane derivatives (2-9) were prepared from labdanediol (1) and their potential as anti-inflammatory agents were evaluated on lipopolysaccharide (LPS)-treated RAW 264.7 macrophages. All compounds were able to inhibit LPS-induced nitric oxide (NO), although compounds 1, 2, 5, 8 and 9 exhibited the most potent effects with a range of IC(50) values of 5-15 microM. Similarly to the inhibitory effects on NO release, these labdane derivatives also inhibited prostaglandin E(2) (PGE(2)) production. However, analysis of cell viability demonstrated that effects on NO release and (PGE(2)) production of compounds 1, 8 and 9 were due to citotoxicity, whereas compound 2 and 5 did not show any effect in the survival of RAW 264.7 macrophages. In addition to these in vitro data, compound 5 also showed anti-inflammatory activity in vivo, when tested in mice. They prevented the extent of swelling in the TPA-induced ear edema model and inhibited MPO activity, showing similar potency to that of the widely used anti-inflammatory drug indomethacin. These results indicate that compound 2 and in particular compound 5 might be used for the design of new anti-inflammatory agents.
Girón
Natalia
N
Departamento de Farmacología, Facultad de Farmacia, Universidad Complutense, Plaza Ramón y Cajal s/n, 28040 Madrid, Spain.
Pérez-Sacau
Elisa
E
López-Fontal
Raquel
R
Amaro-Luis
Juan M
JM
Hortelano
Sonsoles
S
Estevez-Braun
Ana
A
de Las Heras
Beatriz
B
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D015232:Dinoprostone / Q000096:biosynthesis; D004224:Diterpenes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D004487:Edema / Q000188:drug therapy; D020128:Inhibitory Concentration 50; D008297:Male; D051379:Mice; D009569:Nitric Oxide / Q000096:biosynthesis
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004224:Diterpenes; C433017:labdane; C570295:labdanolic acid methyl ester; D009569:Nitric Oxide; D015232:Dinoprostone