Evaluation of labdane derivatives as potential anti-inflammatory agents

Abstract 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 μM. 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.