“Selective Cyclooxygenase 2 inhibitors: synthesis and biological evaluation”
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Date
2019-12-12
Authors
Sawaftah, Hadeel
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Publisher
An-Najah National University
Abstract
Derivatives of diaryl pyrazoles and triazoles were synthesized to produce series of selective COX-2 inhibitors. In order to synthesize the series of these derivatives, Vilsmeier-Haack reaction and click reaction were followed in the synthesis of pyrzoles and triazoles based derivatives respectively. All produced compounds were In vitro evaluated by inhibition studies on COX-1 and COX-2 isozymes. Eleven compounds were successfully synthesized. Five compounds were the most potent and selective on COX-2 isozyme with IC50 values in 0.551–0.002 μM range. In diarylpyrazole derivatives best inhibition was showed by compound 4b with IC50 = 0.017 µM as the N-aromatic rings was substituted with sulfonamide and the other aromatic ring was unsubstituted. However, Compound 4d showed the best selectivity onCOX-2 (IC50 = 0.098 µM, SI = 54.847) as the N-aromatic ring was substituted with sulfonamide and the other aromatic ring was substituted with sulfone. In the diaryltriazole based derivatives, compound 15a was the most potent among the entire synthesized library including the reference compound (Celecoxib) with IC50 = 0.002 µM and SI = 162.5 as the presence of spacer could facilitate binding with extra hydrophobic pocket of COX-2 enzyme. Compounds with a variety of substitutions on pyrazole and triazole cores and different linker lengths are recommended to be synthesized in further studies to evaluate their COX-2 inhibitory activity and selectivity. Moreover, an in vivo anti-inflammatory and cardiotoxicity studies will be managed to support the obtained in vitro results.
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“Selective Cyclooxygenase 2 inhibitors: synthesis and biological evaluation”