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Discovery of (S)-flurbiprofen-based novel azine derivatives as prostaglandin endoperoxide synthase-II inhibitors: Synthesis, in-vivo analgesic, anti-inflammatory activities, and their molecular docking.
- Source :
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Bioorganic chemistry [Bioorg Chem] 2023 Dec; Vol. 141, pp. 106847. Date of Electronic Publication: 2023 Sep 12. - Publication Year :
- 2023
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Abstract
- The anti-inflammatory and analgesic drugs currently used are associated with several adverse effects and found to be highly unsafe for long-term use. Currently, nineteen novel bis-Schiff base derivatives (1-19) of flurbiprofen have been designed, prepared and assessed for in-vivo analgesic, anti-inflammatory and in vivo acute toxicity evaluation. The structures of the acquired compounds were deduced through modern spectroscopic techniques including HR-ESI-MS, <superscript>13</superscript> C-, and <superscript>1</superscript> H NMR. Amongst the series, compounds 7, 9, and 10 attributed potent activities with 93.89, 92.50, and 90.47% decreased edema, respectively compared to flurbiprofen (90.01%), however, compounds 11 and 15 exhibited significant activity of 90.00% decrease. Out of them, fourteen compounds (1-6, 8, 12-14, and 16-19) displayed good activity in the range of 68.96-86.95%. In case of an analgesic study, all the derivatives significantly (p 0.001) increased the pain threshold time particularly compound 7 had the best analgesic effect (24 ± 2.08 s) in comparison with flurbiprofen (21.66 ± 2.02 s) using hot plate test. Similarly, in the acetic acid-induced writhing test, compound 7 determined a potent inhibitory effect (60.47 %) close to flurbiprofen (59.28%). All the synthesized derivatives were found safe up to the dose of 30 mg/kg, in acute toxicity study. On a molecular scale, the synthesized compounds were modeled through a ligand-based pharmacophore study and molecular docking to have insight into the different possible interactions leading to high inhibition levels against the COX-2 enzyme.<br />Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.<br /> (Copyright © 2023 Elsevier Inc. All rights reserved.)
- Subjects :
- Humans
Cyclooxygenase Inhibitors pharmacology
Molecular Docking Simulation
Cyclooxygenase 2
Analgesics pharmacology
Analgesics therapeutic use
Analgesics chemistry
Anti-Inflammatory Agents chemistry
Edema chemically induced
Edema drug therapy
Anti-Inflammatory Agents, Non-Steroidal chemistry
Carrageenan
Flurbiprofen pharmacology
Flurbiprofen chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 1090-2120
- Volume :
- 141
- Database :
- MEDLINE
- Journal :
- Bioorganic chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 37722268
- Full Text :
- https://doi.org/10.1016/j.bioorg.2023.106847