title: N-Caffeoyl serotonin as selective COX-2 inhibitor.
abstract: The inhibitory effects of the synthetic serotonin analogues (1-8) on COX (1 and 2) were evaluated. Two serotonin derivatives (4 and 8) showed inhibitory effect of COX (1 and 2). Especially, 4 exhibited excellent inhibitions on COX-2 with extremely high potency (IC(50)=42.5 μM). The inhibitory activities of cinnamic acid derivatives and serotonin were evaluated to clarify whether inhibitory activities of compound 4 and 8 are due to cinnamic acid moiety or serotonin moiety. Caffeic acid and N-caffeoyl serotonin (4) exhibited selective inhibition of COX-2 compared to aspirin. Comparison caffeic acid with 4 suggested that the linkage of caffeic acid and serotonin enhance COX-2 inhibition. Comparison of structures of caffeic acid and sinapic acid implied that catechol moiety of cinnamic acid derivatives is a major contributing factor for selective inhibition of COX-2. The selective COX-2 inhibitory activity of compound 4 is significant and could be employed as drugs against inflammatory and allergy.
authors.affiliation: Department of Applied Chemistry, Faculty of Science and Engineering, Kinki University, 3-4-1, Kowakae, Higashiosaka-shi, Osaka 577-8502, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Takahashi
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Miyazawa
mesh_terms: D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001241:Aspirin / Q000737:chemistry / Q000494:pharmacology; D001681:Biological Assay; D002109:Caffeic Acids / Q000737:chemistry / Q000494:pharmacology; D002396:Catechols / Q000737:chemistry; D002934:Cinnamates / Q000737:chemistry / Q000494:pharmacology; D003373:Coumaric Acids / Q000737:chemistry / Q000494:pharmacology; D051545:Cyclooxygenase 1 / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D006801:Humans; D012701:Serotonin / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology
chemical_list: D000893:Anti-Inflammatory Agents; D002109:Caffeic Acids; D002396:Catechols; D002934:Cinnamates; D003373:Coumaric Acids; D016861:Cyclooxygenase Inhibitors; C029010:cinnamic acid; D012701:Serotonin; C073734:sinapinic acid; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D001241:Aspirin; C040048:caffeic acid