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

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

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / toxicity
  • Antioxidants
  • Antiviral Agents / chemical synthesis
  • Antiviral Agents / pharmacology*
  • Antiviral Agents / toxicity
  • Catalytic Domain
  • Celecoxib
  • Cell Line, Tumor
  • Cyclooxygenase 2 Inhibitors / chemical synthesis
  • Cyclooxygenase 2 Inhibitors / pharmacology*
  • Cyclooxygenase 2 Inhibitors / toxicity
  • Dose-Response Relationship, Drug
  • Drug Evaluation, Preclinical
  • Edema / chemically induced
  • Edema / drug therapy
  • Female
  • Hepacivirus / enzymology
  • Hindlimb / drug effects
  • Hindlimb / pathology
  • Humans
  • Isothiocyanates / chemistry
  • Lipid Peroxidation / drug effects
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Oxidative Stress / drug effects
  • Protein Binding
  • Pyrazoles / chemical synthesis
  • Pyrazoles / pharmacology*
  • Pyrazoles / toxicity
  • Stomach Ulcer / chemically induced
  • Stomach Ulcer / drug therapy
  • Sulfonamides / chemical synthesis
  • Sulfonamides / pharmacology*
  • Sulfonamides / toxicity
  • Sulfonylurea Compounds / chemical synthesis
  • Sulfonylurea Compounds / pharmacology*
  • Sulfonylurea Compounds / toxicity
  • Thiazolidines / chemical synthesis
  • Thiazolidines / pharmacology*
  • Thiazolidines / toxicity
  • Viral Nonstructural Proteins / antagonists & inhibitors
  • Viral Nonstructural Proteins / chemistry

Substances

  • Antineoplastic Agents
  • Antioxidants
  • Antiviral Agents
  • Cyclooxygenase 2 Inhibitors
  • Isothiocyanates
  • NS-5 protein, hepatitis C virus
  • Pyrazoles
  • Sulfonamides
  • Sulfonylurea Compounds
  • Thiazolidines
  • Viral Nonstructural Proteins
  • Celecoxib