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 -bromoacetate and anhydrous sodium acetate in dry ethanol to N-(substituted aryl/alkylcarbamothioyl)-4-[5-(4-methylphenyl)-3-(trifluoromethyl)-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 OPEN ACCESSMolecules 2013, 18 3596 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.

Different supramolecular architectures mediated by different weak interactions in the crystals of three N-aryl-2,5-dimethoxybenzenesulfonamides

“…The sulfonamide linkage plays a vital role as a key constituent in a number of biologically active molecules. Up to now, sulfonamides have been known to exhibit a wide variety of biological activities, such as antibacterial (Subhakara Reddy et al, 2012; Himel et al, 1971), antifungal (Hanafy et al, 2007), anti-inflammatory ISSN 2053ISSN -2296 # 2017 International Union of Crystallography (Kuçukguzel et al, 2013), antitumor , anticancer (Mansour et al, 2011), anti-HIV (Sahu et al, 2007) and antitubercular activities (Vora & Mehta, 2012). In recent years, extensive research has been carried out on the synthesis and evaluation of the pharmacological activities of molecules containing the sulfonamide moiety for different activities, and have been reported to be important pharmacophores (Mohan et al, 2013).…”

Synthesis of pro-apoptotic indapamide derivatives as anticancer agents

“…1 H NMR and 13 C NMR spectra in DMSO-d 6 were recorded on a BRUKER AVANCE-DPX (Billerica, MA) spectrometer (400 MHz) and chemical shifts are given in ppm downfield from tetramethylsilane (TMS) as an internal standard using DMSO-d 6 as solvent. Data are reported as follows: chemical shift, multiplicity (br.…”

“…This drug was a much weaker one (KI of 2520 nM) inhibitor against CA II 4 . It has been declared that sulfonylthiourea and 4-thiazolidinone structures exhibit antitumoral activity 5,6 . It has been also indicated that some 4-thiazolidinone derivatives selectively inhibit COX-2 enzyme, an important target for some anticancer studies 7 .…”

“…In the present study, indapamide which has indole ring and sulfonamide group was chosen as the starting material and some related 4-thiazolidinone derivatives were synthesized. 4-Chloro-3-({[3-(substituted)-4-oxo-1,3-thiazolidine-2-ylidene] amino}sulfonyl)-N-(2-methyl-2,3-dihydro-1H-indole-1-yl)benzamides (21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31) were synthesized by the addition of ethyl a-bromoacetate and anhydrous sodium acetate in dry ethanol to 4-chloro-3-({[(substitutedamino)carbono-thioyl]amino}sulfonyl)-N-(2-methyl-2,3-dihydro-1H-indole-1-yl)benzamides (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20), which were synthesized by the reaction of alkyl/aryl isothiocyanates with indapamide. The structures of the isolated products were determined by the spectral methods and evaluated anticancer activity for the selected compounds.…”

Anti-cancer and anti-hepatitis C virus NS5B polymerase activity of etodolac 1,2,4-triazoles

“…COX-2 upregulation has also been correlated with the presence of inflammatory cells in hepatocarcinogenesis and tumor angiogenesis in HCC 4 . COX-2 inhibitors have displayed significant antiproliferative effects in many human HCC cell lines 5 . Further, investigations on animal models of liver cancer have shown that NSAIDs, including selective COX-2 inhibitors, exhibit chemopreventive as well as therapeutic effects.…”