I am a
Home I AM A Search Login

Papers of the Week

2020 Apr 26

Bioorg Chem


Design, synthesis, and pharmacological evaluation of novel and selective COX-2 inhibitors based on bumetanide scaffold.


Ibrahim TS, Salem IM, Mostafa SM, El-Sabbagh OI, ElKhamisi MKM, Hegazy L, Elgendy B
Bioorg Chem. 2020 Apr 26; 100:103878.
PMID: 32361486.


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 IC 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.