title: Relationship of chemical structure and anti-inflammatory activity of dihydrocorynantheol and its analogues.
abstract: BACKGROUND
  Dihydrocorynantheol (DHC) is an alkaloid compound isolated from Esenbeckia leiocarpa Engl. that has demonstrated anti-inflammatory properties in experimental models. The aim of this study was to investigate whether the modification of the chemical structure of DHC could alter its anti-inflammatory effect in a mouse model of pleurisy induced by carrageenan.
  
  
  METHODS
  DHC was isolated from Esenbeckia leiocarpa Engl. Capillary electrophoresis, physical characteristics, spectral data produced by infrared analysis and nuclearmagnetic resonance ((1)H and (13)C), and mass spectrometry analysis were used to identify and elucidate DHC structure. The DHC compound was subjected to chemical structural modifications by nucleophilic substitution reactions, yielding five analogous compounds: acetyl (1), p-methylbenzoyl (2), benzoyl (3), p-methoxybenzoyl (4) and p-chlorobenzoyl (5). Swiss mice were used throughout the experiments. Pro-inflammatory parameters leukocyte migration, exudate concentrations and myeloperoxidase (MPO) activity were quantified in the fluid leakage from the mouse pleural cavities at 4 h after pleurisy induction.
  
  
  RESULTS
  DHC and its analogues acetyl, p-methylbenzoyl, benzoyl, p-methoxybenzoyl and p-chlorobenzoyl inhibited total and differential leukocyte migration and MPO activity (p < 0.05). Only DHC significantly decreased the exudate concentrations (p < 0.01).
  
  
  CONCLUSIONS
  DHC was more effective than its analogues as an anti-inflammatory agent in the mouse model of pleurisy induced by carrageenan. We did not determine what physicochemical modifications altered the anti-inflammatory effect of DHC, but this effect may be due to the modifications on the hydroxyl group at carbon 17 of the DHC.
authors.affiliation: Department of Clinical Analysis, Centre of Health Sciences, Federal University of Santa Catarina, Campus Universitário, Trindade, Florianópolis, SC, 88040-970, Brazil. saleh@ccs.ufsc.br.
authors.forename: Patrícia
authors.initials: P
authors.lastname: Pozzatti
authors.forename: Gustavo O
authors.initials: GO
authors.lastname: Dos Reis
authors.forename: Danielle F
authors.initials: DF
authors.lastname: Pereira
authors.forename: Heros
authors.initials: H
authors.lastname: Horst
authors.forename: Leandro
authors.initials: L
authors.lastname: Espindola
authors.forename: Melina
authors.initials: M
authors.lastname: Heller
authors.forename: Gustavo A
authors.initials: GA
authors.lastname: Micke
authors.forename: Moacir G
authors.initials: MG
authors.lastname: Pizzolatti
authors.forename: Tânia S
authors.initials: TS
authors.lastname: Fröde
mesh_terms: D000470:Alkaloids / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000494:pharmacology*; D002351:Carrageenan; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005122:Exudates and Transudates / Q000187:drug effects / Q000276:immunology; D005260:Female; D008297:Male; D051379:Mice; D015394:Molecular Structure; D020556:Neutrophil Infiltration / Q000187:drug effects; D009195:Peroxidase / Q000378:metabolism; D008517:Phytotherapy; D024301:Plant Bark; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D010946:Plants, Medicinal; D010994:Pleura / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D010998:Pleurisy / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D027821:Rutaceae; D013329:Structure-Activity Relationship
chemical_list: D000470:Alkaloids; D000893:Anti-Inflammatory Agents; D010936:Plant Extracts; C007398:dihydrocorynantheol; D002351:Carrageenan; D009195:Peroxidase