Novel benzenesulfonamide and 1,2-benzisothiazol-3(2H)-one-1,1-dioxide derivatives as potential selective COX-2 inhibitors
Autor: | Ehab S. Taher, Abdullah F. Radwan, Tarek S. Ibrahim, Amany M.M. Al-Mahmoudy, Osama I. El-Sabbagh, Mohamed Fares, Khaled Y. Orabi |
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Rok vydání: | 2018 |
Předmět: |
Male
Stereochemistry Pyrazole Ulcer index 01 natural sciences 03 medical and health sciences chemistry.chemical_compound Structure-Activity Relationship Drug Discovery medicine Potency Moiety Animals 030304 developmental biology Pharmacology 0303 health sciences Sulfonamides biology Cyclooxygenase 2 Inhibitors Dose-Response Relationship Drug Molecular Structure 010405 organic chemistry Chemistry Aryl Organic Chemistry Anti-Inflammatory Agents Non-Steroidal Active site General Medicine Triazoles 0104 chemical sciences Rats Molecular Docking Simulation Docking (molecular) Cyclooxygenase 2 biology.protein Celecoxib medicine.drug |
Zdroj: | European journal of medicinal chemistry. 171 |
ISSN: | 1768-3254 |
Popis: | Two new series of 1,2-benzisothiazol-3(2H)-one-1,1-dioxide derivatives containing either five membered heterocyclic rings or aryl hydrazones were synthesized and evaluated for their in vitro COX-1/COX-2 inhibitory activity. In vivo anti-inflammatory evaluation revealed that benzenesulfonamides bearing pyrazole moiety 19, 20 and its cyclized form 23 exhibited the highest anti-inflammatory activity with comparable potency to celecoxib. Furthermore, the ulcerogenic activity evaluation showed that compounds 19, 20 and 23 exerted the minimal ulcer index in comparison to indomethacin as a reference drug. Docking studies of the most selective COX-2 derivatives were also carried out against COX-2 active site. Benzenesulfonamide derivatives 19 and 20 displayed higher predicted binding affinities inside the COX-2 active site. Molecular modelling simulation and drug likeness studies showed good agreement with the obtained biological evaluation. |
Databáze: | OpenAIRE |
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