Synthesis, biological evaluation and molecular modeling of novel selective COX-2 inhibitors: sulfide, sulfoxide, and sulfone derivatives of 1,5-diarylpyrrol-3-substituted scaffold
| Autor: | Maurizio Anzini, Giulia Chemi, Alessia Chelini, Germano Giuliani, Angela Di Capua, Lorenzo Di Cesare Mannelli, Gianluca Giorgi, Concettina La Motta, Annalisa Reale, Massimo Valoti, Antonietta Rossi, Lidia Sautebin, Simona Pace, Marco Paolino, Elena Lucarini, Andrea Cappelli, Simone Brogi, Alessandro Grillo, Carla Ghelardini |
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| Přispěvatelé: | Reale, A., Brogi, S., Chelini, A., Paolino, M., Di Capua, A., Giuliani, G., Cappelli, A., Giorgi, G., Chemi, G., Grillo, A., Valoti, M., Sautebin, L., Rossi, A., Pace, S., La Motta, C., Di Cesare Mannelli, L., Lucarini, E., Ghelardini, C., Anzini, M. |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Male
Molecular model Clinical Biochemistry Anti-Inflammatory Agents Pharmaceutical Science Carrageenan Biochemistry Sulfone Rats Sprague-Dawley chemistry.chemical_compound Mice 1 5-Diarylpyrrole derivative Drug Discovery 1 5-Diarylpyrrole derivatives Anti-inflammatory agents Antinociceptive agents COX-2 inhibitors Molecular modeling Sulfones chemistry.chemical_classification Analgesics Molecular Structure Sulfoxide Biological activity 5-Diarylpyrrole derivatives Molecular Docking Simulation Anti-inflammatory agent Sulfoxides Molecular Medicine Protein Binding Sulfides Cell Line Structure-Activity Relationship In vivo Antinociceptive Agents Animals Humans Pyrroles Rats Wistar COX-2 inhibitor Molecular Biology Inflammation Cyclooxygenase 2 Inhibitors Organic Chemistry Antinociceptive agent Combinatorial chemistry In vitro Enzyme chemistry Cyclooxygenase 2 Drug Design 1 5-Diarylpyrrole derivatives Anti-inflammatory agents Antinociceptive agents COX-2 inhibitors Molecular modeling |
| Popis: | A novel series of 1,5-diarylpyrrol-3-sulfur derivatives (10–12) was synthesized and characterized by NMR and mass spectroscopy and x-ray diffraction. The biological activity of these compounds was evaluated in in vitro and in vivo tests to assess their COX-2 inhibitory activity along with anti-inflammatory and antinociceptive effect. Results showed that the bioisosteric transformation of previously reported alkoxyethyl ethers (9a-c) into the corresponding alkyl thioethers (10a-c) still leads to selective and active compounds being the COX-2 inhibitory activity for most of them in the low nanomolar range. The oxidation products of 10a,b were also investigated and both couple of sulfoxides (11a,b) and sulfones (12a,b) showed an appreciable COX-2 inhibitory activity. Molecular modeling studies were performed to investigate the binding mode of the representative compounds 10b, 11b, and 12b into COX-2 enzyme and to explore the potential site of metabolism of 10a and 10b due to the different in vivo efficacy. Among the developed compounds, compound 10b showed a significant in vivo anti-inflammatory and antinociceptive activity paving the way to develop novel anti-inflammatory drugs. |
| Databáze: | OpenAIRE |
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