New Coumarin Derivatives as Potent Selective COX‐2 Inhibitors: Synthesis, Anti‐Inflammatory, QSAR, and Molecular Modeling Studies. Issue 12 (13th October 2015)

• Record Type: Journal Article
• Authors: Dawood, Dina H.; Batran, Rasha Z.; Farghaly, Thoraya A.; Khedr, Mohammed A.; Abdulla, Mohamed M.
• Is Part Of: Archiv der Pharmazie. Volume 348:Issue 12(2015:Dec.)
• Page Start: 875
• Page End: 888
• Publication Date: 2015-10-13
• Subjects: Anti‐inflammatory -- COX‐2 inhibitors -- Molecular docking -- QSAR -- Thiazolylcoumarin; Pharmaceutical chemistry -- Periodicals; Pharmacology -- Periodicals; 615.19
• DOI: 10.1002/ardp.201500274
• Languages: English
• ISSNs: 0365-6233

Abstract

Abstract : Two new series of coumarin derivatives incorporating thiazoline and thiazolidinone moieties were designed, synthesized, and investigated in vivo for their anti‐inflammatory activities using the carrageenan‐induced rat paw edema model and in vitro for their inhibitory activities against the human cyclooxygenase (COX)‐1 and COX‐2 isoforms. Most of the synthesized compounds demonstrated exceptionally high in vivo anti‐inflammatory activity and displayed superior GI safety profiles (0–7% ulceration) as compared to indomethacin. All the bioactive compounds showed in vitro high affinity and selectivity toward the COX‐2 isoenzyme, compared to the reference celecoxib with IC50 values ranging from 0.31 to 0.78 μM. The ethyl thiosemicarbazone2b, thiazoline derivatives3a, 3b, 5b, 6a, and7f, and the thiazolidinone compounds8b and9a showed the highest in vivo and in vitro anti‐inflammatory activities with remarkable COX‐2 selectivity. Quantitative structure–activity relationship study (QSAR) was done and resulted in a highly predictive power R 2 (0.908). A molecular docking study revealed a relationship between the docking affinity and the biological results. Abstract : A new class of thiazolinyl and thiazolidinonyl‐based coumarin derivatives were designed and synthesized. Activity and molecular docking studies revealed those derivatives with the highest in vivo and in vitro anti‐inflammatory activities. A QSAR model was able to predict the biological activity of some compounds and could be used for predicting the COX‐2 inhibitory activity of new coumarin derivatives.