title: 2-Aryl-3-(2-morpholinoethyl)thiazolidin-4-ones: Synthesis, anti-inflammatory in vivo, cytotoxicity in vitro and molecular docking studies.
abstract: Seven new 4-thiazolidinones bearing the morpholino moiety were easily synthesized by one-pot reactions of 4-(2-aminoethyl)morpholine (2-morpholinoethylamine), arenealdehydes and mercaptoacetic acid refluxing toluene for 19 h with moderate to good yields (45-97%). These novel compounds were fully identified and characterized by NMR spectroscopy and mass spectrometry. Thiazolidin-4-ones in vivo anti-inflammatory activities were determined using a croton oil-induced ear edema model of inflammation in BALB C mice. The best results were found for compounds 4c (49.20 mmol/kg), 4d (49.20 mmol/kg) and 4f (52.48 mmol/kg), which showed the ability to decrease the ear edema in mice by 50%, 48% and 54%, respectively, when compared to the standard drug indomethacin. In addition, the in vitro cytotoxicity activity of thiazolidin-4-ones against Vero cells was also performed and four compounds (4a, 4c, 4d and 4f) showed no toxic effect at 500 μg/mL. A docking simulation of compounds into the 1Q4G (COX-1) and 4PH9 (COX-2) enzymes binding site was conducted. This preliminary result will guide us in for further studies to improve the anti-inflammatory activity.
authors.affiliation: Laboratório de Química Aplicada à Bioativos, Centro de Ciências Químicas, Farmacêuticas e de Alimento, Universidade Federal de Pelotas, Brazil.
authors.forename: Daniela
authors.initials: D
authors.lastname: Pires Gouvea
authors.affiliation: Laboratório de Química Aplicada à Bioativos, Centro de Ciências Químicas, Farmacêuticas e de Alimento, Universidade Federal de Pelotas, Brazil. Electronic address: aleixo.fv@gmail.com.
authors.forename: Flávia Aleixo
authors.initials: FA
authors.lastname: Vasconcellos
authors.affiliation: Laboratório de Química Aplicada à Bioativos, Centro de Ciências Químicas, Farmacêuticas e de Alimento, Universidade Federal de Pelotas, Brazil.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Dos Anjos Berwaldt
authors.affiliation: Laboratório do Grupo de Estudos em Doenças Transmitidas por Animais, Faculdade de Veterinária, Universidade Federal de Pelotas, Brazil.
authors.forename: Amilton Clair Pinto Seixas
authors.initials: AC
authors.lastname: Neto
authors.affiliation: Laboratório de Virologia, Faculdade de Veterinária, Universidade Federal de Pelotas, Brazil.
authors.forename: Gerferson
authors.initials: G
authors.lastname: Fischer
authors.affiliation: Laboratório de Desenvolvimento de Fármacos, Instituto de Química e Faculdade de Ciências Farmacêuticas, Universidade Estadual de Campinas, Brazil.
authors.forename: Renata Parruca
authors.initials: RP
authors.lastname: Sakata
authors.affiliation: Laboratório de Desenvolvimento de Fármacos, Instituto de Química e Faculdade de Ciências Farmacêuticas, Universidade Estadual de Campinas, Brazil.
authors.forename: Wanda Pereira
authors.initials: WP
authors.lastname: Almeida
authors.affiliation: Laboratório de Química Aplicada à Bioativos, Centro de Ciências Químicas, Farmacêuticas e de Alimento, Universidade Federal de Pelotas, Brazil. Electronic address: wjcunico@yahoo.com.br.
authors.forename: Wilson
authors.initials: W
authors.lastname: Cunico
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D002522:Chlorocebus aethiops; D051545:Cyclooxygenase 1 / Q000737:chemistry / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000737:chemistry / Q000378:metabolism; D051379:Mice; D062105:Molecular Docking Simulation; D011487:Protein Conformation; D053778:Thiazolidines / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D014709:Vero Cells
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D053778:Thiazolidines; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2
keywords: Anti-inflammatory activity; Cytotoxicity; Ear edema; Molecular docking; Morpholine; Thiazolidin-4-ones