title: Different effect of two synthetic coumarin-stilbene hybrid compounds on phagocyte activity.
abstract: OBJECTIVE
  Activated phagocytes, generating a variety of powerful inflammatory mediators, such as oxygen and nitrogen species, may participate in oxidative stress-mediated inflammation and organ toxicity. At present, great attention is devoted to the important class of phenolic compounds - coumarins - due to their antiinflammatory/antioxidant activities. We compared two synthetic phenylcoumarins: 7-hydroxy-3-(4´-hydroxyphenyl) coumarin (HHC; 0.01-100 µmol/l) and its hydrogenated analogue: 7-hydroxy-3-(4´-hydroxyphenyl)-3,4-dihydrocoumarin (HHDC; 0.01-100 µmol/l) as their ability to inhibit reactive oxygen species (ROS) generation in human neutrophils and nitric oxide (NO) production by RAW 264.7 macrophages in vitro, with respect to some of their physicochemical characteristics.
  
  
  METHODS
  ROS production was measured with luminol-enhanced chemiluminescence (CL) in the microplate luminometer Immunotech LM-01T, nitrite formation was determined by the Griess reaction - spectrophotometrically. The radical scavenging assays were employed to assess the antiradical activity values. The relevant physico-chemical parameters of the compounds tested, electronic and hydrophobic, were determined experimentally as well as by suitable computational programmes.
  
  
  RESULTS
  Both HHC and HHDC were found to decrease significantly (p<0.01) CL of whole blood stimulated with phorbol myristate acetate (PMA) from the concentration of 1 µmol/l. While HHC significantly inhibited CL stimulated by A23187 and opsonized zymosan (OpZ), HHDC was ineffective. Unlike HHDC, HHC in the concentrations of 10 and 100 µmol/l significantly (p<0.01) reduced NO formation in lipopolysaccharide (LPS) -stimulated murine macrophages RAW 264.7. HHC possessed the higher free radical reducing efficacy in accordance with its more favourable values of electronic parameters in comparison with HHDC.
  
  
  CONCLUSIONS
  Our results show the different inhibitory effects of HHC and HHDC on phagocytic activity that might be the result of their diverse free radical scavenging properties and lipophilicity features.
authors.affiliation: Institute of Experimental Pharmacology and Toxicology, Slovak Academy of Sciences, Bratislava, Slovakia. exfadrak@savba.sk
authors.forename: Katarina
authors.initials: K
authors.lastname: Drabikova
authors.forename: Tomas
authors.initials: T
authors.lastname: Perecko
authors.forename: Radomir
authors.initials: R
authors.lastname: Nosal
authors.forename: Lucia
authors.initials: L
authors.lastname: Rackova
authors.forename: Gabriela
authors.initials: G
authors.lastname: Ambrozova
authors.forename: Antonin
authors.initials: A
authors.lastname: Lojek
authors.forename: Jan
authors.initials: J
authors.lastname: Smidrkal
authors.forename: Juraj
authors.initials: J
authors.lastname: Harmatha
authors.forename: Viera
authors.initials: V
authors.lastname: Jancinova
mesh_terms: D000328:Adult; D000818:Animals; D002460:Cell Line; D003374:Coumarins / Q000494:pharmacology*; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008875:Middle Aged; D023421:Models, Animal; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D010587:Phagocytosis / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013267:Stilbenes / Q000494:pharmacology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D015054:Zymosan / Q000494:pharmacology
chemical_list: D003374:Coumarins; D008070:Lipopolysaccharides; D017382:Reactive Oxygen Species; D013267:Stilbenes; D009569:Nitric Oxide; D015054:Zymosan; D013755:Tetradecanoylphorbol Acetate