Computational Study of Photodegradation Mechanism of Alminoprofen, The Basis for Designing New NSAIDs
Keywords:
alminoprofen, NSAID, decarboxylation, photodegradation, DFT, TD-DFT.Abstract
Alminoprofen (AP) is 2-(4-((2-methlyallyl)amino)phenyl)propanoic acid, or 2-[4-(2-methylprop-2-enylamino)phenyl]propanoic acid. It has a role as a lipoxygenase, a phospholipase A2 and a cyclooxygenase 2 inhibitor. Due to these enzyme’s inhibitions, it is used as anti-inflammatory, anti-rheumatic and anti-pyretic agent in treatment of inflammatory and rheumatic disorders. Because of the AP is belonging to the propionic aromatic acid structure derivatives and is very similar to the ibuprofen molecule and due to the photosensitivity adverse effects related to this group, the present work focuses upon the photosensitivity photodegradation mechanism of AP. This has been done using the HF-DFT/TD-DFT framework by applying the hybrid functional B3LYP level of theory. Similar to other NSAIDs studied previously, the obtained results of AP from the computed energies and properties of various species show that the deprotonated form dominates at physiological pH, is the susceptible species for photodegradation more than the neural form. In addition, the former species will not be able to decarboxylate from a singlet excited states with high efficiency. In contrast, after it undergoes intersystem crossing, the excited triplet state of the deprotonated form will decarboxylate, with very high efficiency. Molecular orbitals, energies of various species, various energy barriers, reactive radical species, the reactions of radical species with macromolecules and more throughout alminoprofen photodegradation mechanism have been discussed in more details in this work.
References
REFERENCES
National Center for Biotechnology Information (2022). PubChem Compound Summary for CID 2097, Alminoprofen. https://pubchem.ncbi.nlm.nih.gov/compound/Al minoprofen.
Raguenes-Nicol C, Russo-Marie F, Domage G, Diab N, Solito E, Dray F, Mace JL, Streichenberger G. Anti-inflammatory mechanism of alminoprofen: action on the phospholipid metabolism pathway. Biochem. Pharmacol. 1999, 57(4):433-43. doi: 10.1016/s0006-2952(98)00312-8.
Fujiyoshi T, Iida H and Hayashi I. Pharmacological profile and mode of action of alminoprofen, a nonsteroidal anti-inflammatory drug. Jap. Pharmacol. Ther. 1990,18: 159–180.
Fujiyoshi T, Iida H, Kuwashima M, Dozen M, Taniguchi N, Ikeda K. Pharmacological Profile of Alminoprofen among Four Writhing Models of Mice Caused by Kaolin, Zymosan, Acetylcholine and Phenylquinone. Journal of Pharmacobio-Dynamics, 1990, 13(1):44-48.
Kojima E, Tamura N, Higashide Y, et al. Effects of alminoprofen on the allergic reactions. Nihon Yakurigaku zasshi. Folia Pharmacologica Japonica. 1990, 96(6):315-321. DOI: 10.1254/fpj.96.6_315.
Maeda E, Uematsu T. The anti-pyretic mechanism of alminoprofen. Nihon Yakurigaku Zasshi. 1991, 98(6):457-66. Japanese. doi: 10.1254/fpj.98.6_457.
Sugahara T, Sakuda M, Yoshida H, Michi KI, kurachi Y, Kanemoto K, Nagumo M. Clinical evaluation of alminoprofen (Minalfen®) on postexodontic pain. Oral Therapeutics and Pharmacology. 1992, 11(3):147-59.
Maeda E, Hujiyoshi T, Uematsu T. Effects of alminoprofen on sodium urate crystal-induced inflammation. Nihon Yakurigaku zasshi. Folia Pharmacologica Japonica. 1991, 98, (6):467-474. DOI: 10.1254/fpj.98.6_467.
Solomon, Daniel H. Nonselective NSAIDs: Overview of adverse effects. UpToDate [internet]. UpToDate Inc.[updated 03.03 2020, cited 03.03 2021] Available from: https://www. uptodate.com (2020).
Kochevar IE. Phototoxicity of Nonsteroidal Inflammatory Drugs: Coincidence or Specific Mechanism? Arch Dermatol. 1989, 125, (6):824–826. doi:10.1001/archderm.1989.01670180096016.
George EA, Baranwal N, Kang JH, Qureshi AA, Drucker AM, Cho E. Photosensitizing Medications and Skin Cancer: A Comprehensive Review. Cancers (Basel). 2021, 12;13(10):2344. doi: 10.3390/cancers13102344.
Costanzo L.L., De Guidi G., Condorelli G., Cambria A., Famà M. Molecular mechanism of naproxen photosensitization in red blood cells. J. Photochem. Photobiol. B. 1989, 3:223–235. doi: 10.1016/1011-1344(89)80064-8.
De Guidi G., Giuffrida S., Condorelli G., Costanzo L.L., Miano P., Sortino S. Molecular mechanism of drug photosensitization. IX. Effect of inorganic ions on DNA cleavage photosensitized by naproxen. Photochem. Photobiol. 1996, 63:455–462. doi: 10.1111/j.1751-1097.1996.tb03069.x.
Mikulec C.D., Rundhaug J.E., Simper M.S., Lubet R.A., Fischer S.M. The chemopreventive efficacies of nonsteroidal anti-inflammatory drugs: The relationship of short-term biomarkers to long-term skin tumor outcome. Cancer Prev. Res. 2013, 6:675–685. doi: 10.1158/1940-6207.CAPR-13-0064.
Gonzalez Maglio D.H., Paz M.L., Ferrari A., Weill F.S., Nieto J., Leoni J. Alterations in skin immune response throughout chronic UVB irradiation-skin cancer development and prevention by naproxen. Photochem. Photobiol. 2010, 86:146–152. doi: 10.1111/j.1751-1097.2009.00623.x.
Becke, A. D., Density-functional thermochemistry .3. the role of exact exchange. Journal of Chemical Physics 1993, 98, (7):5648-5652.
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.
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.
MJT Frisch, G. W. S., H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.; Montgomery, J. A., Jr.; Vreven, T.; Kudin, K. N.; Burant, J. C.; Millam, J. M.; Iyengar, S. S.; Tomasi, J.; Barone, V.; Mennucci, B.; Cossi, M.; Scalmani, G.; Rega, N.; Petersson, G. A.; Nakatsuji, H.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima, T.; Honda, Y.; Kitao, O.; Nakai, H.; Klene, M.; Li, X.; Knox, J. E.; Hratchian, H. P.; Cross, J. B.; Bakken, V.; Adamo, C.; Jaramillo, J.; Gomperts, R.; Stratmann, R. E.; Yazyev, O.; Austin, A. J.; Cammi, R.; Pomelli, C.; Ochterski, J. W.; Ayala, P. Y.; Morokuma, K.; Voth, G. A.; Salvador, P.; Dannenberg, J. J.; Zakrzewski, V. G.; Dapprich, S.; Daniels, A. D.; Strain, M. C.; Farkas, O.; Malick, D. K.; Rabuck, A. D.; Raghavachari, K.; Foresman, J. B.; Ortiz, J. V.; Cui, Q.; Baboul, A. G.; Clifford, S.; Cioslowski, J.; Stefanov, B. B.; Liu, G.; Liashenko, A.; Piskorz, P.; Komaromi, I.; Martin, R. L.; Fox, D. J.; Keith, T.; Al-Laham, M. A.; Peng, C. Y.; Nanayakkara, A.; Challacombe, M.; Gill, P. M. W.; Johnson, B.; Chen, W.; Wong, M. W.; Gonzalez, C.; Pople, J. A. , Gaussian 03, rev. B.02; Gaussian, Inc.: Wallingford, CT, . 2004.
Musa, K. A. K.; Eriksson, L. A., Photodegradation mechanism of the common non-steroid anti-inflammatory drug diclofenac and its carbazole photoproduct. Physical Chemistry Chemical Physics 2009, 11, (22):4601-4610.
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.
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.
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.
Bauernschmitt, R.; Ahlrichs, R., Treatment of electronic excitations within the adiabatic approximation of time dependent density functional theory. Chemical Physics Letters 1996, 256, (4-5):454-464.
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.
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.
Musa, Klefah AK, and Leif A. Eriksson. "Theoretical study of ibuprofen phototoxicity." The Journal of Physical Chemistry B. 2007, 111, (46):13345-13352.
Musa, Klefah AK, Jon M. Matxain, and Leif A. Eriksson. "Mechanism of photoinduced decomposition of ketoprofen." Journal of medicinal chemistry. 2007, 50, (8):1735-1743.
Musa, Klefah AK, and Leif A. Eriksson. "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.
https://amp.chemicalbook.com/ProductChemicalPropertiesCB7885929_EN.htm
Andrew G. Mercader, Mohammad Goodarzi, Pablo R. Duchowicz, Francisco M. Fernandez, Eduardo A. Castro, Predictive qspr study of the dissociation constants of diverse pharmaceutical compounds. Chem Biol Drug Des, 2010, 76:433–440. doi: 10.1111/j.1747-0285.2010.01033.x
https://jpdb.nihs.go.jp/kyokuhou/files/000152738.pdf
Klefah A. K. Musa and Leif A. Eriksson. Theoretical study of the phototoxicity of naproxen and the active form of nabumetone. The Journal of Physical Chemistry A. 2008, 112, (43):10921-10930. DOI: 10.1021/jp805614y.
- Klefah A. K. Musa and Leif A. Eriksson. Photodegradation mechanism of nonsteroidal anti-inflammatory drugs containing thiophene moieties: Suprofen and tiaprofenic acid. The Journal of Physical Chemistry B. 2009, 113, (32):11306-11313. DOI: 10.1021/jp904171p.
Klefah A. K. Musa and Leif A. Eriksson Computational Studies of the Photodegradation Mechanism of the Highly Phototoxic Agent Benoxaprofen. ACS Omega. 2022, 7, (33):29475-29482. DOI: 10.1021/acsomega.2c03118
