title: Synthesis of 2-methyl-3-indolylacetic derivatives as anti-inflammatory agents that inhibit preferentially cyclooxygenase 1 without gastric damage.
abstract: Novel substituted 2-methyl-3-indolylacetic derivatives were synthesized and evaluated for their activity in vitro and in vivo on COX-1 and COX-2. Active compounds were screened to determine their gastrointestinal tolerability in vivo in the rat. Results showed that 3 and 4 preferentially inhibited COX-1 in vitro and in vivo. MD simulations indicated an induced fit for COX-1 but not for COX-2, probably because of a lower plasticity of the latter.
authors.affiliation: Dipartimento di Chimica Farmaceutica e Tossicologica and Dipartimento di Farmacologia Sperimentale, Università di Napoli Federico II, Via D. Montesano 49, 80131 Naples, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Perissutti
authors.forename: Ferdinando
authors.initials: F
authors.lastname: Fiorino
authors.forename: Christian
authors.initials: C
authors.lastname: Renner
authors.forename: Beatrice
authors.initials: B
authors.lastname: Severino
authors.forename: Fiorentina
authors.initials: F
authors.lastname: Roviezzo
authors.forename: Lidia
authors.initials: L
authors.lastname: Sautebin
authors.forename: Antonietta
authors.initials: A
authors.lastname: Rossi
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Cirino
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Santagada
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Caliendo
mesh_terms: D000208:Acute Disease; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D051545:Cyclooxygenase 1 / Q000737:chemistry* / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000737:chemistry* / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D007210:Indoleacetic Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D008565:Membrane Proteins / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D051381:Rats; D013270:Stomach / Q000187:drug effects* / Q000473:pathology; D013329:Structure-Activity Relationship
chemical_list: D000893:Anti-Inflammatory Agents; D016861:Cyclooxygenase Inhibitors; D007210:Indoleacetic Acids; D008565:Membrane Proteins; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human