Photophysical Studies of Oxicam Group of NSAIDs: Piroxicam, Meloxicam and Tenoxicam (original) (raw)
Related papers
Spectroscopic studies of microenvironment dictated structural forms of piroxicam and meloxicam
Long acting non-steroidal anti-inflammatory drugs (NSAIDs) belonging to the oxicam group have attracted special interest because of their diverse biological functions. In this study we present the influence of microenvironment on the spectral properties of two oxicam drugs viz. piroxicam and meloxicam. For the two drugs, a high energy shift of the UV absorption maxima was observed with increasing drug concentrations both in protic solvent like ethanol and aprotic solvent like dimethyl sulfoxide (DMSO). Studies involving variation of percentage volume of water as well as pH, using absorption and steady state fluorescence spectroscopy, allow us to identify the principal species present at different concentrations of the drugs. It is found that even trace quantity of water present in the solvent becomes significant at low concentration of the drug making the water/drug ratio sufficiently large to support the formation of anion. As the concentration of the drug increases, the number of water molecules available per drug molecule decreases and most of the drug molecules face a relatively apolar environment in which zwitterionic/neutral species become predominant. This results in a concentration-dependent high-energy shift of the absorption maximum. This study demonstrates how microenvironments of these drugs guide the nature of the predominant form present in solution. r
Theoretical investigation of the molecular structure and spectroscopic properties of oxicams
Journal of Structural Chemistry, 2017
Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most frequently prescribed drugs and have multiple therapeutic uses. These drugs are predominantly used for the treatment of musculoskeletal diseases because of their analgesic, antipyretic, and antiplatelet activities. Oxicams constitute an interesting class of organic compounds and have been investigated in the search for new analgesic and anti-inflammatory drugs. In the present work, a theoretical investigation of the molecular structure and spectroscopic properties of a series of five oxicams in different solvents was performed using density functional theory (DFT) methods. The geometric optimizations of the oxicams were carried out using the M06 density functional and the CBSB7 basis set. The infrared data were all obtained at the same theoretical level. The UV-Vis absorption and NMR data of some oxicams were calculated using the DFT and CBSB3 basis sets. The analysis of structural parameters, particularly the bond length and spectroscopic data, indicated that interactions occurred between the hydrogen bond types for 4-meloxicam, isoxicam, and normeloxicam. Stereoelectronic interactions caused by the substitution of alkyl groups caused the bond lengths to elongate. Similarly, the substitution of heteroatoms, such as nitrogen, sulfur, or oxygen, increased the bond lengths and angular stresses.
A theoretical and spectroscopic study of conformational structures of piroxicam
Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 2010
Piroxicam (PRX) has been widely studied in an attempt to elucidate the causes and mechanisms of its side effects, mainly the photo-toxicity. In this paper fluorescence spectra in non-protic solvents and different polarities were carried out along with theoretical calculations. Preliminary potential surfaces of the keto and enol forms were obtained at AM1 level of theory providing the most stable conformers, which had their structure re-optimized through the B3LYP/CEP-31G(d,p) method. From the optimized structures, the electronic spectra were calculated using the TD-DFT method in vacuum and including the solvent effect through the PCM method and a single water molecule near PRX. A new potential surface was constructed to the enol tautomer at DFT level and the most stable conformers were submitted to the QST2 calculations. The experimental data showed that in apolar media, the solution fluorescence is raised. Based on conformational analysis for the two tautomers, keto and enol, the results indicated that the PRX-enol is the main tautomer related to the drug fluorescence, which is reinforced by the spectra results, as well as the interconvertion barrier obtained from the QST2 calculations. The results suggest that the PRX one of the enol conformers presents great possibility of involvement in the photo-toxicity mechanisms.
Structure and physicochemical properties of meloxicam, a new NSAID
European Journal of Pharmaceutical Sciences, 1996
The physicochernical properties of meloxicam, a new NSAID. were investigated. Dependent on pit and solvents used, X-ray crystallography showed that meloxicam crystallized in four different prototropic forms; the anion, the acidic enol, the zwitterion and the cation forms. As detemtined" by ~H-and t'C-NMR, meh~xicam in neutral or weakly basic solution exists in the anion form. An equilibrium between the enol and zwitterion fornts, dependent upon solvent polarity, was indicated. Meloxicarn was soluble at neutral pH but became rapidly insoluble with decreasing ptl. At very low ptl its solubility increased, indicating a second pK, value and the existence of a cation species. The very low solubility of nleloxicam in acidic environments suggests it may cause few local gastrointestinal adverse events. The n-octanol-water partition coeflicients (log P values) of meloxicam and other NSAIDs were estimated. At low pH meloxicam was more lipophilic than piroxicam or tenoxicam and similar to ketoprofcn and naproxen.
Photochemistry and Photobiology, 1983
Benoxaprofen [2-(4-chlorophenyl)-cy-methylS -benzoxazole acetic acid] is an antiinflammatory drug that causes acute phototoxicity in many patients. Photolysis studies in organic solvents (ethanol, benzene, dimethylsulfoxide) showed that benoxaprofen underwent both Type I and Type I1 reactions. Irradiation of an anerobic solution of benoxaprofen in ethanol resulted in hydrogen abstraction from the solvent to yield hydroxyethyl and ethoxyl radicals. In the presence of oxygen. superoxide. singlet oxygen and hydroxyethyl radicals were detected. Photolysis of benoxaprofen in air-saturated benzene or dimethylsulfoxide gave superoxide. However, under anerobic conditions the drug yielded a carbon-centered radical in benzene that could not be identified. These findings suggest that both oxygen-dependent and oxygen-independent processes may be important in the phototoxic reactions of benoxaprofen.
Journal of the American Chemical Society, 2018
Gao, J.; et al. "Small molecule interactome mapping by photo-affinity labeling (SIM-PAL) reveals binding site hotspots for the NSAIDs" J. Am. Chem. Soc. 2018. Gao, J.; et al. "Small molecule interactome mapping by photo-affinity labeling (SIM-PAL) reveals binding site hotspots for the NSAIDs" J. Am. Chem. Soc. 2018. S14 General Experimental Procedures. All reactions were performed in single-neck, oven-dried, roundbottomed flasks fitted with rubber septa under a positive pressure of nitrogen, unless otherwise noted. Air-and moisture-sensitive liquids were transferred via syringe or stainless steel cannula. Organic solutions were concentrated by rotary evaporation at 30-33 °C. Normal and reverse phase flash-column chromatography was performed as described by Still and co-workers. 1 Normal phase purifications employ silica gel (60 Å, 40-63 µm particle size) purchased from Silicycle (Quebec, Canada). Analytical thin-layer chromatography (TLC) was performed using glass plates pre-coated with silica gel (0.25 mm, 60 Å pore size) impregnated with a fluorescent indicator (254 nm). TLC plates were visualized by exposure to ultraviolet light (UV), iodine (I 2), and/or submersion in ninhydrin followed by brief heating with a heat gun (10-15 s). Chemical Materials. Commercial solvents and reagents were used as received with the following exceptions. Dichloromethane and N,N-dimethylformamide were purified according to the method of Pangborn and co-workers. 2 Triethylamine was distilled from calcium hydride under an atmosphere of nitrogen immediately before use. 3-aminopiperidine-2,6-dione hydrochloride was obtained from Ark Pharm. RapiGest was prepared according to the method of Lee and co-workers. 3 3-[4-({Bis[(1-tert-butyl-1H-1,2,3-triazol-4-yl)methyl]amino}methyl)-1H-1,2,3-triazol-1-yl]propanol (BTTP) was prepared according to the method of Wu and co-workers. 4 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) was obtained from Sigma Aldrich. Biotin-CA(PEG) 4-alcohol S14 was synthesized according to the method of Tirrell and co-workers. 5
Physicochemical and Structural Properties of Non-Steroidal Anti-inflammatory Oxicams
Helvetica Chimica Acta, 1993
Using the five therapeutic oxicams 1–5, we showed that isosteric replacements result in remarkable changes in the physicochemical and structural properties of congeners. Thus, the acidity of the phenolic OH group is relatively higher in the oxicams containing a pyridinyl moiety, i.e. in piroxicam (1), tenoxicam (2), and lornoxicam, (3), due to their zwitterionic nature. This consequently influences their lipophilicity profile at different ionization states. Furthermore, partitioning behaviour in octan-l-ol/H2O and heptane/H2O systems suggests an internal H-bond between the enolic OH and the amide CO group. The anionic oxicams readily partition into the octanol phase at pH 7.4 and not at all into the heptane phase. Only the partition coefficients of oxicams measured in the heptane/H2O system, but not in the octanol/H2O system, correlate with their transfer across the blood-brain barrier. This implies that only the neutral form of oxicams crosses the blood-brain barrier.
Computational Chemistry, 2019
This work is a contribution of theoretical chemistry to the classification of some non-steroidal anti-inflammatory drugs (NSAIDs). Indeed, research on the efficacy of NSAIDs has shown that no NSAID is recognized as the most efficient anti-inflammatory drug. We have made a theoretical study of diclofenac, bromfenac and amfenac, in order to compare their efficacy from some physicochemical properties. To do this, we used the DFT and TD-DTF methods at the B3LYP/6-311+G(d, p) level theory. The lipophilicity study shows that diclofenac and bromfenac are very lipophilic. Acidity study shows that diclofenac is more acid than bromfenac and amfenac. The results from molecular orbital and the TD-DFT calculations reveal that for the three NSAIDs, the lowest energy transition is due to the excitation from HOMO to LUMO. The absorption energy corresponding to H→L transition is comparable with the energy gap value. Our findings have shown that bromfenac is more reactive than amfenac, which is more reactive than diclofenac.
Journal of The American Academy of Dermatology, 1992
Background: The mechanism of piroxicam-induced photosensitivity is unknown. Itwas first attributed to metabolites of the drug produced in vivo but further photochemical studies disclosed that piroxicam was not stable to light, forming at least two photoproducts. Photosensitivity reactions to droxicam and tenoxicam have been not reported. Objective: The aim of this study was to determine whether piroxicam photoproducts .contribute to the light reactions induced by this drug, to describe a case of droxicam-induced photosensitivity and to study the in vivo photosensitizing potential of tenoxicam. Methods: Patch and photopatch tests with two major photoproducts ofpiroxicam, with different preparations of UVA-preirradiated piroxicam, and with low and high concentrations of tenoxicam were performed in normal volunteers and in piroxicam-photosensitive patients. Phototesting studies were also performed before and after the oral administration of tenoxicam in both groups of subjects.