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Synthesis, anti-inflammatory screening, molecular docking, and COX-1,2/-5-LOX inhibition profile of some novel quinoline derivatives.
- Source :
-
Bioorganic chemistry [Bioorg Chem] 2018 Aug; Vol. 78, pp. 220-235. Date of Electronic Publication: 2018 Mar 20. - Publication Year :
- 2018
-
Abstract
- New quinoline compounds comprising pyrazole scaffold through different amide linkages were synthesized. The synthesized compounds were evaluated for their anti-inflammatory activity. Eight compounds (5c, 11b,c, 12c, 14a,b, 20a and 21a) were found to exhibit promising anti-inflammatory profiles in acute and sub-acute inflammatory models. They were screened for their ulcerogenic activity and none of them showed significant ulcerogenic activity comparable to the reference drug celecoxib and are well tolerated by experimental animals with high safety margin (ALD <subscript>50</subscript> > 0.3 g/kg). Compounds 5c, 11b,c, 12c, 14a,b, 20a and 21a showed significant in vitro LOX inhibitory activity higher than that of zileuton. In vitro COX-1/COX-2 inhibition study revealed that compounds 12c, 14a,b and 20a showed higher selectivity towards COX-2 than COX-1. Among the tested compounds, 12c, 14a and 14b showed the highest inhibitory activity against COX-2 with an IC <subscript>50</subscript> values of 0.1, 0.11 and 0.11 μM respectively. The docking experiments attempted to postulate the binding mode for the most active compounds in the binding site of COX-2 enzymes and confirmed the high selectivity binding towards COX-2 enzyme over COX-1.<br /> (Copyright © 2018 Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Anti-Inflammatory Agents, Non-Steroidal chemical synthesis
Anti-Inflammatory Agents, Non-Steroidal chemistry
Anti-Ulcer Agents chemical synthesis
Anti-Ulcer Agents chemistry
Arachidonate 5-Lipoxygenase metabolism
Cyclooxygenase 1 metabolism
Cyclooxygenase 2 metabolism
Cyclooxygenase Inhibitors chemical synthesis
Cyclooxygenase Inhibitors chemistry
Dose-Response Relationship, Drug
Edema chemically induced
Edema drug therapy
Formaldehyde
Lipoxygenase Inhibitors chemical synthesis
Lipoxygenase Inhibitors chemistry
Male
Molecular Structure
Quinolines chemical synthesis
Quinolines chemistry
Rats
Glycine max enzymology
Stomach Ulcer chemically induced
Stomach Ulcer drug therapy
Structure-Activity Relationship
Anti-Inflammatory Agents, Non-Steroidal pharmacology
Anti-Ulcer Agents pharmacology
Cyclooxygenase Inhibitors pharmacology
Lipoxygenase Inhibitors pharmacology
Molecular Docking Simulation
Quinolines pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1090-2120
- Volume :
- 78
- Database :
- MEDLINE
- Journal :
- Bioorganic chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 29602046
- Full Text :
- https://doi.org/10.1016/j.bioorg.2018.03.023