Synthesis and biological evaluation of fluorinated 1,5-diarylpyrrole-3-alkoxyethyl ether derivatives as selective COX-2 inhibitors endowed with anti-inflammatory activity
| Autor: | Antonietta Rossi, Antonio Giordani, Giovanna Poce, Andrea Cappelli, Angela Di Capua, Lidia Sautebin, Mariangela Biava, Carla Ghelardini, Margherita Brindisi, Simona Pace, Simone Brogi, Maurizio Anzini, Gianluca Giorgi, Claudia Sticozzi, Giuseppe Valacchi, Lorenzo Di Cesare Mannelli |
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| Přispěvatelé: | 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 |
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
Models
Molecular 0301 basic medicine Skin Neoplasms Halogenation Cell Human skin Antiproliferative activity chemistry.chemical_compound 0302 clinical medicine Drug Discovery Edema 5-diarylpyrrole derivatives Skin Anti-inflammatory agents Analgesics 1 5-diarylpyrrole derivative Anti-Inflammatory Agents Non-Steroidal General Medicine Anti-inflammatory agent medicine.anatomical_structure Hyperalgesia 030220 oncology & carcinogenesis Molecular modelling medicine.symptom Keratinocyte Adult medicine.drug_class Stereochemistry 1 5-diarylpyrrole derivatives Antinociceptive agents COX-2 inhibitors Animals Antineoplastic Agents Cell Line Cell Proliferation Cyclooxygenase 2 Cyclooxygenase 2 Inhibitors Humans Pyrroles Rats Drug Discovery3003 Pharmaceutical Science Organic Chemistry Pharmacology Ether Anti-inflammatory NO 03 medical and health sciences medicine Antinociceptive Agents COX-2 inhibitor Antinociceptive agent HaCaT 030104 developmental biology chemistry anti-inflammatory agents antinociceptive agents antiproliferative activity cox-2 inhibitors molecular modelling drug discovery3003 pharmaceutical science organic chemistry pharmacology |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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