title: Anti-inflammatory and antinociceptive activities of indole-imidazolidine derivatives.
abstract: Non-steroidal anti-inflammatory drugs (NSAIDs) represent a group of approximately 50 different medicines that are widely prescribed for the management of inflammation and that exhibit variable anti-inflammatory, anti-pyretic and analgesic activities. Most NSAIDs also exhibit a shared set of adverse effects, particularly related to gastrointestinal complications; thus, the development of new drugs for the treatment of chronic inflammation and pain continues to be an issue of high interest. Hydantoin and indole derivatives are reported to possess various pharmacological effects, including anti-inflammatory and analgesic activities. Therefore, the aim of this study was to evaluate the potential anti-inflammatory and antinociceptive activities of hybrid molecules containing imidazole and indole nuclei. The anti-inflammatory activities of 5-(1H-Indol-3-yl-methylene)-2-thioxo-imidazolidin-4-one (LPSF/NN-56) and 3-(4-Bromo-benzyl)-5-(1H-indol-3-yl-methylene)-2thioxo-imidazolidin-4-one (LPSF/NN-52) were evaluated using air pouch and carrageenan-induced peritonitis models as well as an acetic acid-induced vascular permeability model followed by IL-1β and TNF-α quantification. To evaluate the antinociceptive activities of the compounds, acetic acid-induced nociception, formalin and hot plate tests were also performed. The anti-inflammatory activities of the compounds were evidenced by a reduction in both leukocyte migration and the release of TNF-α and IL-1β in air pouch and peritonitis models. Upon acetic acid-induced nociception, a decrease in the level of abdominal writhing in the groups treated with LPSF/NN-52 (52.1%) or LPSF/NN-56 (63.1%) was observed. However, in the hot plate test, none of the derivatives tested exhibited an inhibition of nociception. These results indicate that the compounds tested exhibited promising anti-inflammatory and antinociceptive activities that likely involved the modulation of the immune system.
authors.affiliation: Departamento de Antibióticos, Centro de Ciências Biológicas, Universidade Federal de Pernambuco, Rua Prof. Moraes Rêgo, s/n, Cidade Universitária, Recife/PE, Brazil.
authors.forename: Aline Stamford Henrique da Silva
authors.initials: AS
authors.lastname: Guerra
authors.forename: Diana Jussara do Nascimento
authors.initials: DJ
authors.lastname: Malta
authors.forename: Luana Priscilla Morais
authors.initials: LP
authors.lastname: Laranjeira
authors.forename: Maria Bernadete Souza
authors.initials: MB
authors.lastname: Maia
authors.forename: Nathália Cavalcanti
authors.initials: NC
authors.lastname: Colaço
authors.forename: Maria do Carmo Alves
authors.initials: Mdo C
authors.lastname: de Lima
authors.forename: Suely Lins
authors.initials: SL
authors.lastname: Galdino
authors.forename: Ivan da Rocha
authors.initials: Ida R
authors.lastname: Pitta
authors.forename: Teresinha
authors.initials: T
authors.lastname: Gonçalves-Silva
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry / Q000627:therapeutic use*; D001522:Behavior, Animal / Q000187:drug effects; D002199:Capillary Permeability / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D048289:Imidazolidines / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry* / Q000627:therapeutic use; D007211:Indoles / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry* / Q000627:therapeutic use; D053583:Interleukin-1beta / Q000276:immunology; D008297:Male; D051379:Mice; D010146:Pain / Q000188:drug therapy* / Q000503:physiopathology; D010147:Pain Measurement; D010538:Peritonitis / Q000188:drug therapy / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: C571661:3-(4-bromobenzyl)-5-(1H-indol-3-yl-methylene)-2-thioxoimidazolidin-4-one; C571660:5-(1H-indol-3-yl-methylene)-2-thioxo-imidazolidin-4-one; D000894:Anti-Inflammatory Agents, Non-Steroidal; D048289:Imidazolidines; D007211:Indoles; D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha