Mechanism of photoinduced photodegradation of piroxicam, the way to design new drugs of piroxicam derivatives
Abstract
Initiation of photodegradation mechanism and subsequently pathways of non steroidal anti inflammatory drugs (NSAID), piroxicam are studied by means of computational quantum chemistry at the DFT-B3LYP/6-311++G(d, p) level. The results show that the drug readily absorbs radiation from the UV region of the spectrum. The proposed initiation process of piroxicam photodegradation, in which the reaction between molecular oxygen and piroxicam in presence of light occurs, required passing an energy barrier computed to be ~21 kcal/mol in solvent. The formed intermediate species from the former reaction undergoes spontaneously intramolecular rearrangements (mainly dioxetane ring opening) once it is optimized in its triplet state. The net of these rearrangements is carboxylic acid compound which also has a capability to absorb radiation from UV region and forms various photoproducts depending upon the site of cleavage. Moreover, energetic of these species, the computed UV spectra by time-dependent density functional theory (TD-DFT) and possible reactive singlet oxygen species formation in different pathways are explained in detail in this manuscript.
References
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2. de Souza, K. F.; Martins, J. A.; Pessine, F. B. T.; Custodio, R., A theoretical and spectroscopic study of conformational structures of piroxicam. Spectrochimica Acta Part a-Molecular and Biomolecular Spectroscopy 2010, 75, (2), 901-907.
3. Pal, S.; Bindu, P.; DubeyB, P. K.; Chakraborty, S.; Mukherjee, A. K., Synthesis and structure analysis of cyclodehydration product of piroxicam: A metabolite detected in dogs and monkeys. European Journal of Medicinal Chemistry 2009, 44, (8), 3368-3371.
4. Schiantarelli, P.; Acerbi, D.; Bovis, G., Some pharmacokinetic properties and bioavailability by oral and rectal route of piroxicam in rodents and in man. Arzneimittel-Forschung/Drug Research 1981, 31-1, (1), 92-97.
5. Michotte, Y.; Vanklaveren, H. P.; Detaevernier, M. R.; Gusdorf, C. F.; Vanhaelst, L., Bioequivalence of 2 formulations of piroxicam. Arzneimittel-Forschung/Drug Research 1991, 41-1, (3), 244-246.
6. Gehad, G. M.; Nadia, E. A. E., Preparation and spectroscopic characterisation of metal complexes of piroxicam. Vibrational Spectroscopy 2004, 36, (1), 97-104.
7. Banerjee, R.; Sarkar, M., Spectroscopic studies of micro environment dictated structural forms of piroxicam and meloxicam. Journal of Luminescence 2002, 99, (3), 255-263.
8. Musa, K. A. K.; Matxain, J. M.; Eriksson, L. A., Mechanism of photoinduced decomposition of ketoprofen. Journal of Medicinal Chemistry 2007, 50, (8), 1735-1743.
9. Musa, K. A. K.; Eriksson, L. A., Theoretical study of ibuprofen phototoxicity. Journal of Physical Chemistry B 2007, 111, (46), 13345-13352.
10. Musa, K. A. K.; Eriksson, L. A., Theoretical Study of the Phototoxicity of Naproxen and the Active Form of Nabumetone. Journal of Physical Chemistry A 2008, 112, (43), 10921-10930.
11. Musa, K. A. K.; Eriksson, L. A., Photochemical and photophysical properties, and photodegradation mechanism, of the non-steroid anti-inflammatory drug Flurbiprofen. Journal of Photochemistry and Photobiology a-Chemistry 2009, 202, (1), 48-56.
12. Miranda, M. A.; Vargas, F.; Serrano, G., Photodegradation of piroxicam under aerobic conditions - the photochemical keys of the piroxicam enigma. Journal of Photochemistry and Photobiology B-Biology 1991, 8, (2), 199-202.
13. Becke, A. D., Density-functional thermochemistry. 3. The role of exact exchange. Journal of Chemical Physics 1993, 98, (7), 5648-5652.
14. Stephens, P. J.; Devlin, F. J.; Chabalowski, C. F.; Frisch, M. J., Ab-initio calculation of vibrational absorption and circular-dichroism spectra using density-functional force-fields. Journal of Physical Chemistry 1994, 98, (45), 11623-11627.
15. Lee, C. T.; Yang, W. T.; Parr, R. G., Development of the colle-salvetti correlation-energy formula into a functional of the electron-density. Physical Review B 1988, 37, (2), 785-789.
16. Cances, E.; Mennucci, B.; Tomasi, J., A new integral equation formalism for the polarizable continuum model: Theoretical background and applications to isotropic and anisotropic dielectrics. Journal of Chemical Physics 1997, 107, (8), 3032-3041.
17. Mennucci, B.; Tomasi, J., Continuum solvation models: A new approach to the problem of solute's charge distribution and cavity boundaries. Journal of Chemical Physics 1997, 106, (12), 5151-5158.
18. Cossi, M.; Scalmani, G.; Rega, N.; Barone, V., New developments in the polarizable continuum model for quantum mechanical and classical calculations on molecules in solution. Journal of Chemical Physics 2002, 117, (1), 43-54.
19. Casida, M. E., Time-dependent density functional response theory for molecules. In Recent advances in density functional methods, Part 1. Ed: Chong, D.P. ed.; World Scientific: Singapore, 1995; p 155-192.
20. Stratmann, R. E.; Scuseria, G. E.; Frisch, M. J., An efficient implementation of time-dependent density-functional theory for the calculation of excitation energies of large molecules. Journal of Chemical Physics 1998, 109, (19), 8218-8224.
21. Casida, M. E.; Jamorski, C.; Casida, K. C.; Salahub, D. R., Molecular excitation energies to high-lying bound states from time-dependent density-functional response theory: Characterization and correction of the time-dependent local density approximation ionization threshold. Journal of Chemical Physics 1998, 108, (11), 4439-4449.
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23. Western, A.; Vancamp, J. R.; Bensasson, R.; Land, E. J.; Kochevar, I. E., Involvement of singlet oxygen in the phototoxicity mechanism for a metabolite of piroxicam. Photochemistry and Photobiology 1987, 46, (4), 469-475.
24. Becker, R. S.; Chakravorti, S.; Yoon, M. J., Photochemical and Photophysical properties of piroxicam and benoxaprofen in various solvents. Photochemistry and Photobiology 1990, 51, (2), 151-154.
25. Figueiredo, A.; Ribeiro, C. A. F.; Goncalo, S.; Caldeira, M. M.; Poiaresbaptista, A.; Teixeira, F., Piroxicam-induced photosensitivity. Contact Dermatitis 1987, 17, (2), 73-79.
26. Yoon, M. J.; Choi, H. N.; Kwon, H. W.; Park, K. H., Solvent dependence of absorption and fluorescence-spectra of piroxicam – a possible intramolecular proton-transfer in the excited-state. Bulletin of the Korean Chemical Society 1988, 9, (3), 171-175.
27. Nagaoka, S.; Hirota, N.; Sumitani, M.; Yoshihara, K., Investigation of the dynamic processed of the excited-states of ortho-hydroxybenzaldehyde and ortho-hydroxyacetophenone by emission and picosecond spectroscopy. Journal of the American Chemical Society 1983, 105, (13), 4220-4226.
28. Andrade, S. M.; Costa, S. M. B., Hydrogen bonding effects in the photophysics of a drug, Piroxicam, in homogeneous media and dioxane-water mixtures. Physical Chemistry Chemical Physics 1999, 1, (18), 4213-4218.
29. Lissi, E. A.; Encinas, M. V.; Lemp, E.; Rubio, M. A., Singlet oxygen O2(∆g) bimolecular processes – solvent and comparatmentalization effects. Chemical Reviews 1993, 93, (2), 699-
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2018-04-26
How to Cite
Mechanism of photoinduced photodegradation of piroxicam, the way to design new drugs of piroxicam derivatives. (2018). Lebda Medical Journal, 4(1), 154–167. Retrieved from https://lebmedj.elmergib.edu.ly/index.php/LMJ/article/view/75
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