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Synthesis and biological evaluation of fluorinated 1,5-diarylpyrrole-3-alkoxyethyl ether derivatives as selective COX-2 inhibitors endowed with anti-inflammatory activity.
Di Capua, Angela; Sticozzi, Claudia; Brogi, Simone; Brindisi, Margherita; Cappelli, Andrea; Sautebin, Lidia; Rossi, Antonietta; Pace, Simona; Ghelardini, Carla; Di Cesare Mannelli, Lorenzo; Valacchi, Giuseppe; Giorgi, Gianluca; Giordani, Antonio; Poce, Giovanna; Biava, Mariangela; Anzini, Maurizio.
Afiliación
  • Di Capua A; Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Via Aldo Moro 2, 53100 Siena, Italy.
  • Sticozzi C; Department of Life Sciences and Biotechnology, University of Ferrara, Via Luigi Borsari 46, 44121 Ferrara, Italy.
  • Brogi S; Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Via Aldo Moro 2, 53100 Siena, Italy.
  • Brindisi M; Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Via Aldo Moro 2, 53100 Siena, Italy.
  • Cappelli A; Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Via Aldo Moro 2, 53100 Siena, Italy.
  • Sautebin L; Department of Pharmacy, University of Naples "Federico II", Via D. Montesano 49, I-80131, Napoli, Italy.
  • Rossi A; Department of Pharmacy, University of Naples "Federico II", Via D. Montesano 49, I-80131, Napoli, Italy.
  • Pace S; Department of Pharmacy, University of Naples "Federico II", Via D. Montesano 49, I-80131, Napoli, Italy.
  • Ghelardini C; Department of Pharmacology Neuroscience, Psychology, Drug Research and Child Health - Neurofarba, Pharmacology and Toxicology Section, University of Florence, Viale G. Pieraccini 6, I-50139 Firenze, Italy.
  • Di Cesare Mannelli L; Department of Pharmacology Neuroscience, Psychology, Drug Research and Child Health - Neurofarba, Pharmacology and Toxicology Section, University of Florence, Viale G. Pieraccini 6, I-50139 Firenze, Italy.
  • Valacchi G; Department of Life Sciences and Biotechnology, University of Ferrara, Via Luigi Borsari 46, 44121 Ferrara, Italy; Department of Food and Nutrition, Kyung Hee University, Seoul, South Korea.
  • Giorgi G; Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Via Aldo Moro 2, 53100 Siena, Italy.
  • Giordani A; Rottapharm Biotech, Via Valosa di Sopra 7, 20052 Monza, Italy.
  • Poce G; Department of Chemical Studies and Technologies of Drugs, University of Rome "La Sapienza", Piazzale Aldo Moro 5, 00185 Roma, Italy.
  • Biava M; Department of Chemical Studies and Technologies of Drugs, University of Rome "La Sapienza", Piazzale Aldo Moro 5, 00185 Roma, Italy.
  • Anzini M; Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Via Aldo Moro 2, 53100 Siena, Italy. Electronic address: maurizio.anzini@unisi.it.
Eur J Med Chem ; 109: 99-106, 2016 Feb 15.
Article en En | MEDLINE | ID: mdl-26774035
A series of substituted 1,5-diarylpyrrole-3-alkoxyethyl ethers were previously synthesized and the potential anti-inflammatory and antinociceptive activities of these compounds were evaluated in vivo. The compounds displayed a very good activity against both carrageenan-induced hyperalgesia and oedema in the rat paw test. Therefore, in a very preliminary test, compounds (8a,b) showed antiproliferative activity in the HaCaT (aneuploid immortal keratinocyte from adult human skin) cell models. On these basis, our research continued with the synthesis of fluorinated derivatives (8c,d, 9b-d, and 10b-d) with the aim of improving the pharmacokinetic profile of the previous active compounds. Substitution of a hydrogen atom by a fluorine atom may change the conformational preferences of the molecules due to stereoelectronic effects and also fluorine atom may be able to exert the metabolic obstruction reducing the "first-pass effect". Compound 10b exhibited a prominent in vivo anti-inflammatory and antinociceptive activities, in addition its antiproliferative power in an in vitro model of human skin cancer is herein described.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Pirroles / Antiinflamatorios no Esteroideos / Inhibidores de la Ciclooxigenasa 2 Límite: Adult / Animals / Humans Idioma: En Revista: Eur J Med Chem Año: 2016 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Francia

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Pirroles / Antiinflamatorios no Esteroideos / Inhibidores de la Ciclooxigenasa 2 Límite: Adult / Animals / Humans Idioma: En Revista: Eur J Med Chem Año: 2016 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Francia