1. Synthesis and Characterization of Celecoxib Derivatives as Possible Anti-Inflammatory, Analgesic, Antioxidant, Anticancer and Anti-HCV Agents
- Author
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Ozge Cevik, Derya Özsavcı, Şule Gürsoy, Göknur Aktay, Amartya Basu, Neerja Kaushik-Basu, Azize Şener, Şükriye Küçükgüzel, Ozlem Bingol Ozakpinar, Sevil Aydin, Inci Coskun, Tanaji T. Talele, Kucukguzel, S. Guniz, Coskun, Inci, Aydin, Sevil, Aktay, Goknur, Gursoy, Sule, Cevik, Ozge, Ozakpinar, Ozlem Bingol, Ozsavci, Derya, Sener, Azize, Kaushik-Basu, Neerja, Basu, Amartya, Talele, Tanaji T., [Kucukguzel, S. Guniz -- Coskun, Inci -- Aydin, Sevil] Marmara Univ, Fac Pharm, Dept Pharmaceut Chem, TR-34668 Istanbul, Turkey -- [Aktay, Goknur -- Gursoy, Sule] Inonu Univ, Fac Pharm, Dept Pharmacol, TR-44280 Malatya, Turkey -- [Cevik, Ozge -- Ozakpinar, Ozlem Bingol -- Ozsavci, Derya -- Sener, Azize] Marmara Univ, Fac Pharm, Dept Biochem, TR-34668 Istanbul, Turkey -- [Cevik, Ozge] Cumhuriyet Univ, Fac Pharm, Dept Biochem, TR-58140 Sivas, Turkey -- [Kaushik-Basu, Neerja -- Basu, Amartya] UMDNJ New Jersey Med Sch, Dept Biochem & Mol Biol, Newark, NJ 07103 USA -- [Talele, Tanaji T.] St Johns Univ, Dept Pharmaceut Sci, Coll Pharm & Allied Hlth Profess, Jamaica, NY 11439 USA, Cevik, Ozge -- 0000-0002-9325-3757, and AKTAY, Goknur -- 0000-0002-1646-8674
- Subjects
Male ,LIPID PEROXIDES ,Antioxidant ,medicine.medical_treatment ,Drug Evaluation, Preclinical ,Pharmaceutical Science ,Hepacivirus ,Viral Nonstructural Proteins ,HEPATITIS-C VIRUS ,01 natural sciences ,Medicinal chemistry ,Antioxidants ,Analytical Chemistry ,Mice ,chemistry.chemical_compound ,0302 clinical medicine ,Isothiocyanates ,Catalytic Domain ,HEPATOCELLULAR-CARCINOMA ,Drug Discovery ,Edema ,Organic chemistry ,anti-inflammatory ,PAW EDEMA ,chemistry.chemical_classification ,Mice, Inbred BALB C ,Sulfonamides ,Trifluoromethyl ,celecoxib ,PROSTAGLANDIN ,NS5B POLYMERASE ,POLYMERASE INHIBITORS ,Hindlimb ,3. Good health ,sulfonylthiourea ,Chemistry (miscellaneous) ,030220 oncology & carcinogenesis ,ACID ,Thiazolidines ,Molecular Medicine ,Female ,Protein Binding ,medicine.drug ,medicine.drug_class ,Analgesic ,Antineoplastic Agents ,anticancer ,Antiviral Agents ,Article ,Anti-inflammatory ,lcsh:QD241-441 ,hepatitis C NS5B ,CYCLOOXYGENASE-2 ,03 medical and health sciences ,lcsh:Organic chemistry ,Cell Line, Tumor ,medicine ,Animals ,Humans ,Stomach Ulcer ,Physical and Theoretical Chemistry ,Alkyl ,Ethanol ,Cyclooxygenase 2 Inhibitors ,Dose-Response Relationship, Drug ,010405 organic chemistry ,Aryl ,Organic Chemistry ,RING-SYSTEMS ,0104 chemical sciences ,Oxidative Stress ,Sulfonylurea Compounds ,chemistry ,Celecoxib ,Pyrazoles ,Lipid Peroxidation - Abstract
WOS: 000316611700079, PubMed ID: 23519201, 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 alpha-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., Research Fund of Marmara University [SAG-A-310510-0175]; National Institute of Health [CA153147], We wish to thank the National Cancer Institute for in vitro pharmacological screening. This work was generously supported by the Research Fund of Marmara University, project number: SAG-A-310510-0175 to S. G. K. HCV NS5B inhibition studies were supported by the National Institute of Health Research Grant CA153147 to N.K.-B. The authors are grateful to Jurgen Gross from the Institute of Organic Chemistry, University of Heidelberg, for his generous help on obtaining HR-EI mass spectra of the synthesized compounds.
- Published
- 2013