title: 3D-QSAR and preliminary evaluation of anti-inflammatory activity of series of N-pyrrolylcarboxylic acids.
abstract: The present study focuses on development of new potential inhibitors of cyclooxygenase-2 (COX-2): series of N-pyrrolylcarboxylic acids. 3D-QSAR (Quantitative Structure-Activity Relationship) CoMFA (Comparative Molecular Field Analysis) and CoMSIA (Comparative Molecular Similarity Index Analysis) models for predicting inhibitory activities against COX-1 and COX-2 as well as for evaluating in vivo anti-inflammatory activity were obtained and used for preliminary screening of new anti-inflammatory N-pyrrolylcarboxylic acids. Nine compounds were selected for in vivo testing and evaluated for their potency to decrease carrageenin-induced edema in rats. The compounds were applied i.p. at doses 20 mg/kg and 40 mg/kg and p.o. at doses 10 mg/kg and 40 mg/kg. Six compounds showed more than 70% protection of the edema. Indomethacin (2 mg/kg i.p.), used as a reference drug, possessed 54% anti-inflammatory activity under similar experimental conditions.
authors.affiliation: Centre of Biomedical Engineering, Bulgarian Academy of Sciences, Bulgaria.
authors.forename: Iglika
authors.initials: I
authors.lastname: Lessigiarska
authors.forename: Atanas
authors.initials: A
authors.lastname: Nankov
authors.forename: Adriana
authors.initials: A
authors.lastname: Bocheva
authors.forename: Ilza
authors.initials: I
authors.lastname: Pajeva
authors.forename: Atanas
authors.initials: A
authors.lastname: Bijev
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001665:Binding Sites; D002351:Carrageenan / Q000737:chemistry; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D007213:Indomethacin / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011758:Pyrroles / Q000138:chemical synthesis*; D021281:Quantitative Structure-Activity Relationship; D051381:Rats; D013329:Structure-Activity Relationship
chemical_list: D000893:Anti-Inflammatory Agents; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D011758:Pyrroles; D002351:Carrageenan; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D007213:Indomethacin