Premium
Effects of Geranyloxycinnamic Acids on COX‐2 and i NOS Functionalities in LPS‐Stimulated U937 Mononuclear Cells
Author(s) -
Genovese Salvatore,
Fiorito Serena,
Taddeo Vito Alessandro,
Epifano Francesco,
Paciotti Roberto,
Coletti Cecilia,
Franceschelli Sara,
Speranza Lorenza,
Ferrone Alessio,
Felaco Mario,
Patruno Antonia
Publication year - 2016
Publication title -
chemistryselect
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.437
H-Index - 34
ISSN - 2365-6549
DOI - 10.1002/slct.201601091
Subject(s) - chemistry , stereochemistry , arginine , nitro , nitric oxide , peripheral blood mononuclear cell , side chain , biochemistry , amino acid , in vitro , organic chemistry , alkyl , polymer
A series of naturally occurring and semisynthetic O ‐geranyl cinnamic acids and their conjugates with the i NOS inhibitor N ω ‐nitro‐L‐arginine methyl ester have been synthesized and evaluated for their effects on expressions of COX‐2 and i NOS, antioxidant activity, and PGE 2 and NO production in LPS‐stimulated U937 mononuclear cells. All adducts showed little or no effect on i NOS functionality in terms of NO release. A much more significant activity has been recorded on PGE 2 biosynthesis for which the sample substituted with a ‐NO 2 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 (IC 50 =0.71 μM and 0.1 μM 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.