title: Design, synthesis and pharmacobiological evaluation of novel acrylic acid derivatives acting as lipoxygenase and cyclooxygenase-1 inhibitors with antioxidant and anti-inflammatory activities.
abstract: A series of novel acrylic acid derivatives bearing at the 3 position thienyl, furfuryl and 3,5-ditert-butyl-4-hydroxyphenyl substituents have been designed, synthesized and tested as potential dual lipoxygenase/cyclooxygenase-1 (LOX/COX-1) inhibitors and as antioxidant and anti-inflammatory agents. Some compounds have shown moderate antioxidant and COX-1 inhibitory activities, very good anti-inflammatory activity and an inhibition of soybean lipoxygenase (LOX) higher than caffeic acid. In particular, compound 4I disclosed a moderate in vitro LOX inhibition with an IC(50) = 100 μM whereas compounds 1I and 2II exhibited the best, albeit poor, activity as COX-1 inhibition (75% inhibition at 100 μM). Good radical scavenging properties were shown by compounds 4I, 3I and 1II. Docking simulations performed on LOX inhibitor 4I and COX-1 inhibitor 1I indicated that hydrophobic key interactions may govern the enzyme-inhibitor binding.
authors.affiliation: Department of Pharmaceutical Chemistry, School of Pharmacy, Aristotelian University of Thessaloniki, Thessaloniki 54124, Greece. epontiki@pharm.auth.gr
authors.forename: Eleni
authors.initials: E
authors.lastname: Pontiki
authors.forename: Dimitra
authors.initials: D
authors.lastname: Hadjipavlou-Litina
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Litinas
authors.forename: Orazio
authors.initials: O
authors.lastname: Nicolotti
authors.forename: Angelo
authors.initials: A
authors.lastname: Carotti
mesh_terms: D000179:Acrylates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D000975:Antioxidants / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D001665:Binding Sites; D051545:Cyclooxygenase 1 / Q000737:chemistry / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D015195:Drug Design; D005260:Female; D016166:Free Radical Scavengers / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D007249:Inflammation / Q000188:drug therapy; D008084:Lipoxygenase / Q000737:chemistry / Q000378:metabolism; D016859:Lipoxygenase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008958:Models, Molecular; D011487:Protein Conformation; D051381:Rats; D013025:Glycine max / Q000201:enzymology
chemical_list: D000179:Acrylates; D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D016861:Cyclooxygenase Inhibitors; D016166:Free Radical Scavengers; D016859:Lipoxygenase Inhibitors; D008084:Lipoxygenase; D051545:Cyclooxygenase 1; C036658:acrylic acid