title: Synthesis and characterization of celecoxib derivatives as possible anti-inflammatory, analgesic, antioxidant, anticancer and anti-HCV agents.
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.
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Marmara University, Haydarpaşa, 34668 İstanbul, Turkey. gkucukguzel@marmara.edu.tr
authors.forename: Ş Güniz
authors.initials: ŞG
authors.lastname: Küçükgüzel
authors.forename: İnci
authors.initials: İ
authors.lastname: Coşkun
authors.forename: Sevil
authors.initials: S
authors.lastname: Aydın
authors.forename: Göknur
authors.initials: G
authors.lastname: Aktay
authors.forename: Şule
authors.initials: Ş
authors.lastname: Gürsoy
authors.forename: Özge
authors.initials: Ö
authors.lastname: Çevik
authors.forename: Özlem Bingöl
authors.initials: ÖB
authors.lastname: Özakpınar
authors.forename: Derya
authors.initials: D
authors.lastname: Özsavcı
authors.forename: Azize
authors.initials: A
authors.lastname: Şener
authors.forename: Neerja
authors.initials: N
authors.lastname: Kaushik-Basu
authors.forename: Amartya
authors.initials: A
authors.lastname: Basu
authors.forename: Tanaji T
authors.initials: TT
authors.lastname: Talele
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology* / Q000633:toxicity; D000975:Antioxidants; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000494:pharmacology* / Q000633:toxicity; D020134:Catalytic Domain; D000068579:Celecoxib; D045744:Cell Line, Tumor; D052246:Cyclooxygenase 2 Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology* / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D005260:Female; D016174:Hepacivirus / Q000201:enzymology; D006614:Hindlimb / Q000187:drug effects / Q000473:pathology; D006801:Humans; D017879:Isothiocyanates / Q000737:chemistry; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018384:Oxidative Stress / Q000187:drug effects; D011485:Protein Binding; D011720:Pyrazoles / Q000138:chemical synthesis / Q000494:pharmacology* / Q000633:toxicity; D013276:Stomach Ulcer / Q000139:chemically induced / Q000188:drug therapy; D013449:Sulfonamides / Q000138:chemical synthesis / Q000494:pharmacology* / Q000633:toxicity; D013453:Sulfonylurea Compounds / Q000138:chemical synthesis / Q000494:pharmacology* / Q000633:toxicity; D053778:Thiazolidines / Q000138:chemical synthesis / Q000494:pharmacology* / Q000633:toxicity; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry; D012324:RNA-Dependent RNA Polymerase
chemical_list: D000970:Antineoplastic Agents; D000975:Antioxidants; D000998:Antiviral Agents; D000068579:Celecoxib; D052246:Cyclooxygenase 2 Inhibitors; D017879:Isothiocyanates; D011720:Pyrazoles; D013449:Sulfonamides; D013453:Sulfonylurea Compounds; D053778:Thiazolidines; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase