A series of naturally occurring and semisynthetic O-geranyl cinnamic acids and their conjugates with the iNOS inhibitor N-omega-nitro-L-arginine methyl ester have been synthesized and evaluated for their effects on expressions of COX-2 and iNOS, antioxidant activity, and PGE2 and NO production in LPSstimulated U937 mononuclear cells. All adducts showed little or no effect on iNOS functionality in terms of NO release. A much more significant activity has been recorded on PGE2 biosynthesis for which the sample substituted with a -NO2 group in position 3 of the aromatic ring revealed an effect in the nM range both for the L-NAME conjugated product and the parent compound (IC50= 0.71 mu M and 0.1 mu M respectively). Preliminary docking studies have been carried out to clarify the mechanism of COX-2 inhibition, and they suggest that the geranyloxy side chain is likely to play an important role for the observed activity and that structural modifications are able to tune such effects.

Effects of Geranyloxycinnamic Acids on COX-2 and iNOS Functionalities in LPS-Stimulated U937 Mononuclear Cells

GENOVESE, Salvatore
Primo
;
FIORITO, SERENA
Secondo
;
TADDEO, VITO ALESSANDRO;EPIFANO, Francesco;PACIOTTI, ROBERTO;COLETTI, Cecilia;FRANCESCHELLI, SARA;SPERANZA, Lorenza;FERRONE, ALESSIO;FELACO, Mario;PATRUNO, ANTONIA
Ultimo
2016-01-01

Abstract

A series of naturally occurring and semisynthetic O-geranyl cinnamic acids and their conjugates with the iNOS inhibitor N-omega-nitro-L-arginine methyl ester have been synthesized and evaluated for their effects on expressions of COX-2 and iNOS, antioxidant activity, and PGE2 and NO production in LPSstimulated U937 mononuclear cells. All adducts showed little or no effect on iNOS functionality in terms of NO release. A much more significant activity has been recorded on PGE2 biosynthesis for which the sample substituted with a -NO2 group in position 3 of the aromatic ring revealed an effect in the nM range both for the L-NAME conjugated product and the parent compound (IC50= 0.71 mu M and 0.1 mu M respectively). Preliminary docking studies have been carried out to clarify the mechanism of COX-2 inhibition, and they suggest that the geranyloxy side chain is likely to play an important role for the observed activity and that structural modifications are able to tune such effects.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11564/654740
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