title: Inhibition of COX-1 activity and COX-2 expression by 3-(4'-geranyloxy-3'-methoxyphenyl)-2-trans propenoic acid and its semi-synthetic derivatives.
abstract: Oxyprenylated naturally occurring cinnamic acids displayed efficient and promising biological activities. Aim of this study was to characterize the effects of 3-(4'-geranyl-3'-methoxy)phenyl-2-trans propenoic acid and its selected semi-synthetic analogues, on COX-2 expression and activity, and on COX-1 activity, in purified systems or in whole cell systems. The anti-inflammatory activity of title compounds (1) was tested as inhibition of COX-2 on isolated monocytes stimulated with LPS (10 μg/ml). COX-2 expression was completely suppressed when monocytes were incubated with 100 μM of 3-(4'-geranyl-3'-methoxy)phenyl-2-trans propenoic acid (1) or 3-(4'-isopentenyloxy)phenyl-2-trans propenoic acid (4). Moreover compounds (1) and (4) inhibit dose-dependently LPS-induced COX-2 expression.
authors.affiliation: Dipartimento di Scienze del Farmaco, Università 'G. D'Annunzio' di Chieti-Pescara, Via dei Vestini 31, 66100 Chieti Scalo (CH), Italy. s.genovese@unich.it
authors.forename: Salvatore
authors.initials: S
authors.lastname: Genovese
authors.forename: Massimo
authors.initials: M
authors.lastname: Curini
authors.forename: Paolo
authors.initials: P
authors.lastname: Gresele
authors.forename: Teresa
authors.initials: T
authors.lastname: Corazzi
authors.forename: Francesco
authors.initials: F
authors.lastname: Epifano
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000906:Antibodies / Q000276:immunology; D002934:Cinnamates / Q000737:chemistry; D051545:Cyclooxygenase 1 / Q000276:immunology / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004224:Diterpenes / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D006801:Humans; D020128:Inhibitory Concentration 50; D008070:Lipopolysaccharides / Q000276:immunology; D058990:Molecular Targeted Therapy; D009000:Monocytes / Q000187:drug effects / Q000201:enzymology / Q000276:immunology; D011422:Propionates / Q000737:chemistry / Q000494:pharmacology*; D011817:Rabbits; D013329:Structure-Activity Relationship
chemical_list: C506371:3-(4'-geranyloxy-3'-methoxyphenyl)-2-trans-propenoic acid; D000893:Anti-Inflammatory Agents; D000906:Antibodies; D002934:Cinnamates; D016861:Cyclooxygenase Inhibitors; D004224:Diterpenes; D008070:Lipopolysaccharides; D011422:Propionates; C029010:cinnamic acid; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2