Design, synthesis, and pharmacological evaluation of novel and selective COX-2 inhibitors based on bumetanide scaffold
Document Type
Article
Publication Title
Bioorganic Chemistry
Abstract
Herein, we describe the design and synthesis of new benzenesulfonamide derivatives as selective COX-2 inhibitors based on bumetanide scaffold. Benzenesulfonamides bearing both the pyrazole 6b and the triazoles 9a, 9c were good inhibitors of COX-2 with IC50 values of 0.32, 0.28 and 0.17 µM, respectively. These benzenesulfonamides 6b, 9a and 9c exhibited a higher selectivity index than the reference drug celecoxib. Molecular modeling study showed that incorporation of bumetanide led to a unique binding mode that is most likely the reason for the observed significant COX-2 selectivity. The anti-inflammatory activity of synthesized compounds revealed that triazoles 9a and 9c demonstrated higher efficacy than celecoxib upon using in vivo carrageenan-induced rat paw edema model. Most of the prepared compounds possess low ulcerogenic potential when administered orally. Therefore, these compounds have a great potential to be developed as safe therapeutics for inflammation, pain, and other diseases where COX-2 plays important role in their pathophysiology.
DOI
10.1016/j.bioorg.2020.103878
Publication Date
7-1-2020
Recommended Citation
Ibrahim, Tarek S.; Salem, Ibrahim M.; Mostafa, Samia M.; El-Sabbagh, Osama I.; ElKhamisi, Mohamed K.M.; Hegazy, Lamees; and Elgendy, Bahaa, "Design, synthesis, and pharmacological evaluation of novel and selective COX-2 inhibitors based on bumetanide scaffold" (2020). Pharmaceutical and Administrative Sciences Faculty Publications. 89.
https://doi.org/10.1016/j.bioorg.2020.103878
https://collections.uhsp.edu/pharm-admin-sciences_pubs/89