title: Pteridine-2,4-diamine derivatives as radical scavengers and inhibitors of lipoxygenase that can possess anti-inflammatory properties.
abstract: BACKGROUND
  Reactive oxygen species are associated with inflammation implicated in cancer, atherosclerosis and autoimmune diseases. The complex nature of inflammation and of oxidative stress suggests that dual-target agents may be effective in combating diseases involving reactive oxygen species.
  
  
  RESULTS
  A novel series of N-substituted 2,4-diaminopteridines has been synthesized and evaluated as antioxidants in several assays. Many exhibited potent lipid antioxidant properties, and some are inhibitors of soybean lipoxygenase, IC50 values extending down to 100 nM for both targets. Several pteridine derivatives showed efficacy at 0.01 mmol/kg with little tissue damage in a rat model of colitis. 2-(4-methylpiperazin-1-yl)-N-(thiophen-2-ylmethyl)pteridin-4-amine (18f) at 0.01 mmol/kg exhibited potent anti-inflammatory activity (reduction by 41%).
  
  
  CONCLUSIONS
  The 2,4-diaminopteridine core represents a new scaffold for lipoxygenase inhibition as well as sustaining anti-inflammatory properties.
authors.affiliation: Christopher Ingold Laboratories, Department of Chemistry, University College London, 20 Gordon Street, London WC1H OAJ, UK.|Department of Pharmaceutical Chemistry, Faculty of Health Sciences, School of Pharmacy, Aristotle University of Thessaloniki, Thessaloniki, 54124, Greece.
authors.forename: Eleni
authors.initials: E
authors.lastname: Pontiki
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Health Sciences, School of Pharmacy, Aristotle University of Thessaloniki, Thessaloniki, 54124, Greece.
authors.forename: Dimitra
authors.initials: D
authors.lastname: Hadjipavlou-Litina
authors.affiliation: Rome Center for Molecular Design, Dipartimento di Chimica e Tecnologie del Farmaco, Sapienza University of Rome, 00185 Rome, Italy.
authors.forename: Alexandros
authors.initials: A
authors.lastname: Patsilinakos
authors.affiliation: Christopher Ingold Laboratories, Department of Chemistry, University College London, 20 Gordon Street, London WC1H OAJ, UK.
authors.forename: Trang M
authors.initials: TM
authors.lastname: Tran
authors.affiliation: Christopher Ingold Laboratories, Department of Chemistry, University College London, 20 Gordon Street, London WC1H OAJ, UK.
authors.forename: Charles M
authors.initials: CM
authors.lastname: Marson
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry* / Q000378:metabolism / Q000627:therapeutic use; D001665:Binding Sites; D003092:Colitis / Q000188:drug therapy / Q000473:pathology; D003959:Diamines / Q000737:chemistry*; D004195:Disease Models, Animal; D004487:Edema / Q000473:pathology / Q000517:prevention & control; D016166:Free Radical Scavengers / Q000737:chemistry* / Q000378:metabolism; D008084:Lipoxygenase / Q000737:chemistry* / Q000378:metabolism; D016859:Lipoxygenase Inhibitors / Q000737:chemistry* / Q000378:metabolism / Q000627:therapeutic use; D008297:Male; D062105:Molecular Docking Simulation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011621:Pteridines / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use; D051381:Rats; D017382:Reactive Oxygen Species / Q000737:chemistry / Q000378:metabolism; D013025:Glycine max / Q000201:enzymology
chemical_list: C115021:2,4-diaminopteridine; D000893:Anti-Inflammatory Agents; D003959:Diamines; D016166:Free Radical Scavengers; D016859:Lipoxygenase Inhibitors; D011621:Pteridines; D017382:Reactive Oxygen Species; D008084:Lipoxygenase