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. 2013 Mar 21;18(3):3595-614.
doi: 10.3390/molecules18033595.

Synthesis and Characterization of Celecoxib Derivatives as Possible Anti-Inflammatory, Analgesic, Antioxidant, Anticancer and anti-HCV Agents

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Free PMC article

Synthesis and Characterization of Celecoxib Derivatives as Possible Anti-Inflammatory, Analgesic, Antioxidant, Anticancer and anti-HCV Agents

Ş Güniz Küçükgüzel et al. Molecules. .
Free PMC article

Abstract

A series of novel N-(3-substituted aryl/alkyl-4-oxo-1,3-thiazolidin-2-ylidene)-4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamides 2a-e were synthesized by the addition of ethyl a-bromoacetate and anhydrous sodium acetate in dry ethanol to N-(substituted aryl/alkylcarbamothioyl)-4-[5-(4-methylphenyl)-3-(trifluoro-methyl)-1H-pyrazol-1-yl]benzene sulfonamides 1a-e, which were synthesized by the reaction of alkyl/aryl isothiocyanates with celecoxib. The structures of the isolated products were determined by spectral methods and their anti-inflammatory, analgesic, antioxidant, anticancer and anti-HCV NS5B RNA-dependent RNA polymerase (RdRp) activities evaluated. The compounds were also tested for gastric toxicity and selected compound 1a was screened for its anticancer activity against 60 human tumor cell lines. These investigations revealed that compound 1a exhibited anti-inflammatory and analgesic activities and further did not cause tissue damage in liver, kidney, colon and brain compared to untreated controls or celecoxib. Compounds 1c and 1d displayed modest inhibition of HCV NS5B RdRp activity. In conclusion, N-(ethylcarbamothioyl)-4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide (1a) may have the potential to be developed into a therapeutic agent.

Figures

Figure 1
Figure 1
Pyrazofurin and SC-560.
Scheme 1
Scheme 1
Synthesis of celecoxib derivatives 1a1e, 2a2e.
Figure 2
Figure 2
XP-Glide predicted binding mode of compound 1c within palm pocket-I of NS5B. Important amino acids contacting compound 1c are depicted as stick model with the atoms colored as carbon—green, hydrogen—white, nitrogen—blue, oxygen—red and sulfur—yellow. Compound 1c is shown as ball and stick model with the same color scheme as above except carbon atoms are represented in cyan and fluoro atoms in green color. The dotted black line indicates hydrogen bonding interaction whereas the dotted red line indicates cation-pi interaction with distances in Å.

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