Anti-inflammatory Drugs Tenoxicam Research Articles

Mixed-ligand complexes of tenoxicam drug with some transition metal ions in presence of 2,2′-bipyridine: Synthesis, spectroscopic characterization, thermal analysis, density functional theory and in vitro cytotoxic activity

The Preparation and characterization of Cr(III), Fe(III), Co(II), Ni(II), Cu(II) and Y(III) mixed ligand metal complexes with the effective anti-inflammatory drug tenoxicam (Ten) and 2,2′-bipyridine (Bipy) have been informed in this study by using elemental analyses, FT-IR, UV–Vis., 1H NMR, mass spectra, thermal analyses (TGA, DTG), molar conductance and magnetic moment. FT-IR and UV–Vis. spectra proved that Ten acts as a neutral bidentate ligand chelated to the metal ions via the pyridine-N and oxygen of carbonyl group of the amide moiety and Bipy chelated through the nitrogen atoms. The thermodynamic parameters (E*, ΔS∗, ΔH∗ and ΔG∗) were calculated by using Coats–Redfern and Horowitz– Metzger method from DTG curves. The antimicrobial activity for all compounds against various species of bacteria and fungi was investigated and the results ensured that Fe(III) complex is more active than all other complexes. The DFT calculations were carried out to understand the optimized molecular geometry for the compounds. All studied complexes considered as soft respect to the Ten, with σ value varied from 11.236 to 16.949 eV and equal to 8.772eV for Ten. The anticancer activity was screened against cell culture of HCT-116 (human colorectal carcinoma), HepG2 (human hepatocellular carcinoma) and MCF-7 (human breast adenocarcinoma) for all compounds.

Electroanalytical Determination of the Antiinflammatory Drug Tenoxicam in Pharmaceutical Dosage Forms.

The electro-oxidation behavior of the non-steroidal anti-inflammatory drug tenoxicam (TX) was studied on multiwalled carbon nanotube (MWCNT)-modified glassy carbon electrode (GCE) by cyclic voltammetry, differential pulse voltammetry (DPV), and square wave voltammetry (SWV). The GCE was modified with MWCNT for sensitive determination of TX by voltammetric methods. The current peaks for TX occurred at around 0.520 V for DPV and 0.570 V for SWV when the potential was scanned in the positive direction. The oxidation process of TX showed irreversible and diffusion-controlled behavior. The linear responses were obtained in the range from 2×10-7 to 1×10-5 M with the limit of detection (LOD) 1.43×10-9 for DPV and from 8×10-9 to 8×10-6 with the LOD 9.97×10-10 for SWV in 1 M acetate buffer solution at pH 5.5. Fully validated DPV and SWV were successfully applied for the determination of TX from pharmaceutical dosage form and yielded satisfying results.

Solubility and thermodynamics of tenoxicam in (PEG-400 + water) binary solvent systems at different temperatures

In this study, the solubility and thermodynamics of an anti-inflammatory drug tenoxicam (TNX) in various [polyethylene glycol-400 (PEG-400)+water] binary solvent systems was measured at temperatures T=(298.15 to 323.15) K and pressure p=0.1MPa. The solubilities of TNX were measured by an isothermal method and correlated with calculated ones. The mole fraction solubility of TNX was recorded highest in neat PEG-400 (3.50×10−2 at T=323.15K) and lowest in neat water (4.13×10−6 at T=298.15K) over the entire temperature range investigated. Thermodynamic studies on solubility of TNX indicated an endothermic, spontaneous and entropy driven dissolution behavior of TNX in all binary solvent systems investigated. The solubility experimental data of this research work could be useful in preformulation studies and formulation development of TNX.

Complex formation of the anti-inflammatory drugs tenoxicam and piroxicam with Fe(III) in methanol and acetone

A spectrophotometric study of the chemical coordination of two nonsteroidal anti-inflammatory drugs (tenoxicam and piroxicam) with Fe(III) has been undertaken in methanol in order to determine the stoichiometry and formation constants of the formed complexes, 1 : 1 and 1 : 2 stoichiometric ratios [Fe(III) : oxicam]. The formation constants determined with the aid of the program SQUAD, at 293 K in methanol, are: Fe(tenox), log β 11 = 4.71 ± 0.03; Fe(tenox)2, log β 12 = 8.57 ± 0.04; Fe(pirox), log β 11 = 5.54 ± 0.09; Fe(pirox)2, log β 12 = 9.75 ±0.08. However, the study in acetone gave rise to complexes with completely different stoichiometric ratios with polynuclear species [dimers of Fe(III)]. The formation constants determined with the aid of program SQUAD, at 293 K in acetone, are: Fe2(tenox), log β 21 =9.04 ± 0.03; Fe2(tenox)2, log β 22 = 14.75 ± 0.06; Fe2(tenox)3, log β 23 = 18.45 ± 0.07; Fe2(pirox), log β 21 = 9.06 ± 0.30; Fe2(pirox)2, log β 22 = 14.77 ± 0.09; Fe2(tenox)3, log β 23 = 18.48 ± 0.40. Besides the well-known effect of the solvent on thermodynamic constants, the stoichiometry seems to be strongly driven by the nature of the solvent.

Uranyl and transition metal chelates of tenoxicam. Crystal structures of trans,trans -[Co(II)(Hten)2(dmso)2], trans , trans -[Zn(II)(Hten)2(dmso)2] and cis , cis -[UO2(VI)(Hten)2(H2O)] · 2C2H5OH

The synthesis and characterization of ternary Fe(III)- (1), Co(II)- (2), Ni(II)- (3), Cu(II)- (4), Zn(II)- (5) and UO2(VI)- (6) chelates with the potent anti-inflammatory drug tenoxicam (H2ten) and (dl-alanine, Hala) are reported. All complexes are octahedral except Cu(II) and Zn(II) chelates, which are tetrahedral, and U-atoms in the uranyl chelates have a pentagonal-bipyramidal coordination sphere. The ternary Co(II) and Zn(II) complexes dissociate in dmso where orange and yellow crystals of trans,trans-[Co(II)(Hten)2(dmso)2] (8) and trans,trans-[Zn(II)(Hten)2(dmso)2] (9), respectively, were obtained. Crystallization of the binary uranyl chelate (7) from ethanol afforded the ethanol solvate cis,cis-[UO2(VI)(Hten)2(H2O)] · 2C2H5OH (7a). trans,trans-[Co(II)(Hten)2(dmso)2] (8) and trans,trans-[Zn(II)(Hten)2(dmso)2] (9) crystallize in the monoclinic space group P21/n while 7a crystallizes in the triclinic space group . The kinetics of the thermal decompositions for 1, 3, 4, 6 and 7 were studied and the thermodynamic parameters E*, ΔH*, ΔS* and ΔG* evaluated.

Novel Chemical Transformations of Tenoxicam

Both N- and O-substituted derivatives of the anti-inflammatory drug tenoxicam (= 4-hydroxy-2-methyl-N-(pyridin-2-yl)-2H-thieno[2,3-e] [1,2]thiazine-3-carboxamide 1,1-dioxide; 1) were synthesized, and various chemical transformations were investigated. Both selective hydrolysis and reaction of 1′-N-methyltenoxicam (5) with a variety of N-nucleophiles were performed (Scheme 1). Also, five new 4-O-acyl derivatives 10 were prepared as potential prodrugs (Scheme 2). The 4-chloro derivatives of 1 and its analog 8 could be successfully transformed into the novel tetra- and tricyclic ring systems 12 and 13, respectively, the latter being a conformationally restricted 1,5-diaryl-pyrazole designed as a potential COX-2 inhibitor.

Speciation study of the anti-inflammatory drug tenoxicam (Htenox) with Cu(II): X-ray crystal structure of [Cu(tenox) 2(py) 2]·EtOH

A speciation study was carried out in aqueous solution of the anti-inflammatory drug tenoxicam (Htenox), under quasi-physiological conditions (temperature of 37 °C and ionic strength 0.15 M NaCl) in order to determine the acidity constants from spectrophotometric studies, the p K a values found being p K 1=1.143±0.008 and p K 2=4.970±0.004. Subsequently, the spectrophotometrical speciation of the different complexes of Cu(II) with the drug was performed under the same conditions of temperature and ionic strength, observing the formation of Cu(Htenox) 2 2+ with log β 212=20.05±0.01, Cu(tenox) 2 with log β 012=13.6±0.1, Cu(Htenox) 2+ with log β 111=10.52±0.08, as well as Cu(tenox) + with log β 011=7.0±0.2, all of them in solution, and solid species Cu(tenox) 2(s) with an estimated value of log β 012(s)≈18.7. The crystalline structure of the complex [Cu(tenox) 2(py) 2]·EtOH, was also determined, and it was observed that tenoxicam employs the oxygen of the amide group and the pyridyl nitrogen to bond to the cation.

Organotin-Drug Interactions. Organotin Adducts of Tenoxicam: Synthesis and Characterization of the First Organotin Complex of Tenoxicam

The synthesis and spectral characterization of the novel organotin complexes [SnBu2(ten)] (1) and [SnBu2(Hten)2] (2) of the potent and widely used anti-inflammatory drug tenoxicam (H2ten) are reported. A crystal-structure determination of 1 showed that, in this complex, the ligand is doubly deprotonated at the hydroxy O-atom and the amide N-atom and is coordinated to the SnBu2 fragment via four- and six-membered chelate rings. An extended network of Sn−O−Sn, C−H⋅⋅⋅O and C−H⋅⋅⋅π contacts lead to aggregation and a supramolecular assembly. Potentiometric titrations in nonaqueous solutions support the ionization of the drug by removal of the second H-atom, the amide H-atom, in the presence of the diorganotin(IV) fragment. The Ka values of the poorly H2O-soluble drug tenoxicam were obtained spectrophotometrically in aqueous solutions of constant ionic strength.

SIMULTANEOUS HIGH PERFORMANCE LIQUID CHROMATOGRAPHIC ANALYSIS OF NON-STEROIDAL ANTI-INFLAMMATORY OXICAMS IN PHARMACEUTICAL PREPARATIONS

A simple and rapid isocratic high-performance liquid chromatographic method has been developed for the simultaneous analysis of the non-steroidal anti-inflammatory drugs tenoxicam, piroxicam, meloxicam, and lornoxicam using isoxicam as an internal standard. The analyte was chromatographed using a Lichrosphere RP18 column, a Tris acetic acid buffer-tetrabutylammonium reagent-tetrahydrofuran-acetonitrile as the mobile phase, and UV detection at 360 nm. The separation obtained was very good. The method was applied to pharmaceutical formulations containing a single active ingredient and was shown to be linear, sensible, accurate, and reproducible. A very small modification of the mobile phase enabled the separation of tenoxicam, piroxicam, isoxicam, cinnoxicam,meloxicam, and lornoxicam with symmetrical and well resolved peaks.

Using Difference Spectrophotometry to Study the Influence of Different Ions and Buffer Systems on Drug Protein Binding

Difference spectrophotometry was used to investigate the effect of different ions and buffer systems on the binding of the anti-inflammatory drug tenoxicam to human serum albumin (HSA). Chloride anions, as well as sodium cations, were found to decrease the binding affinity. The effect of chloride ions was greater on the primary binding constant K1, while sodium ions had a greater effect on the secondary binding constant K2. The number of binding sites n1 n2 were not affected except at 0.12% HSA, for which the presence of sodium ions halved n2. Potassium ions significantly increased K1. The presence of potassium instead of sodium ions increased binding affinity at lower HSA concentrations. The number of binding sites n1 and n2 were fewer in presence of potassium than in the presence of sodium ions except at 0.12% HSA. The divalent calcium and magnesium cations increased the binding affinity of HSA to tenoxicam, with a greater effect on K1. The effect of magnesium ions on K1 occurred when the MgCl2 concentration was increased to 3 and 9 mM, with the former seeming to be a critical concentration. The number of primary binding sites n1 was not affected by calcium ions, but was halved by 1 mM MgCl2. Both calcium and magnesium cations decreased n2, which was halved when the concentration of either cation was increased to 9 mM. The effect of buffer systems on tenoxicam binding to HSA was dependent on HSA concentration. The value of K1 was higher in Sorensen's phosphate buffer than in Tris [tris(hydroxymethyl) aminomethane HCl] buffer when the HSA concentration was 0.04% and 0.16%, while the reverse was observed at 0.08% and 0.12% HSA. The other binding parameters (K2, n1, and n2) were higher in Sorensen's phosphate than in Tris buffer. However; at certain HSA concentrations, the values of such parameters were comparable in both buffer systems.

Modulation of Receptor Bound Urokinase-type Plasminogen Activator on Human Monocytes by Non-steroidal Antiinflammatory Drugs

It has been shown previously that cell surface bound fibrinolytic activity on human monocytes is significantly increased in patients with rheumatoid arthritis (RA) as compared to monocytes from healthy volunteers. Studies on the modulation of receptor-bound urokinase type plasminogen activator on peripheral blood monocytes of patients with RA showed that tenoxicam, a non-steroidal antiinflammatory drug with long half life and good tissue permeability, is able to downregulate the total number of urokinase receptors. Furthermore the degree of endogenous occupation of the urokinase receptor was significantly decreased in post-treatment monocytes. These data provide evidence that the non-steroidal antiinflammatory drug tenoxicam is able to downregulate cell bound fibrinolytic activity, known to contribute to pronounced degradation of cartilage and connective tissue in patients with RA.

Metal complexes of anti-inflammatory drugs. Part IV. Tenoxicam complexes of manganese(II), iron(III), cobalt(II), nickel(II) and copper(II)

The preparation, spectroscopic and magnetic properties are reported for complexes of manganese(II), iron(III), cobalt(II), nickel(II) and copper(II) with the anti-inflammatory drug tenoxicam. In all the complexes studied the tenoxicam acts as a chelate monoanionic ligand with coordination involving the enolate oxygen atom and the carbonyl oxygen atom of the amide group. The complexes appear to have an octahedral stereochemistry involving two chelate tenoxicam ligands in the case of divalent central metal ions and three chelate tenoxicam ligands in the iron(III) complex. The manganese(II) and copper(II) complexes exhibit marked superoxide dismutase activity in the nitroblue tetrazolium assay.