The Mechanisms and Kinetics of Radical Scavenging Activity of Edaravone: A Computational Insight
Main Article Content
Abstract
Edaravone (EDV, 3-methyl-1-phenyl-2-pyrazolin-5-one) is a neuroprotective drug that has been used to treat acute stroke caused by cerebral thrombosis and embolism. Studies showed that EDV could be used to treat diseases related to oxidizing agents; however, the activity has not been fully studied yet. In this study, the free radical scavenging activity of EDV was investigated by thermodynamic and kinetic calculations. The results showed that EDV exhibited good HOO• radical scavenging activity in an aqueous medium at pH = 7.40 (koverall(HOO) = 8.58´107 M-1 s-1) through the electron transfer mechanism of the anion state. In contrast, this activity was insignificant in non-polar environments. EDV also exhibited excellent antiradical activity against HO·, CH3O·, CH3OO·, O2·-, NO2, SO4·-, N3· and DPPH radicals in the aqueous solution. Thus, it appears to suggest that EDV is a promising radical scavenger in polar environments.
Keywords:
Edaravone, DFT study, antiradical activity, antioxidant, kinetics.
References
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[5] A. P. González, A. Galano, On the Outstanding Antioxidant Capacity of Edaravone Derivatives through Single Electron Transfer Reactions, J. Phys. Chem. B, Vol. 116, No. 3, 2012, pp. 1180-1188, https://doi.org/10.1021/jp209930y.
[6] A. Galano, J. R. A. Idaboy, Kinetics of Radical-Molecule Reactions in Aqueous Solution: A Benchmark Study of the Performance of Density Functional Methods, J. Comput. Chem., Vol. 35, No. 28, 2014, pp. 2019-2026,
https://doi.org/10.1002/jcc.23715.
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https://doi.org/10.1021/jp7109127.
[8] E. Dzib, J. L. Cabellos, F. O. Chi, S. Pan, A. Galano, G. Merino, Eyringpy: A Program for Computing Rate Constants in the Gas Phase and in Solution, Int. J. Quantum Chem., Vol. 119, No. 2, 2019, pp. e25686, https://doi.org/10.1002/qua.25686.
[9] A. Galano, J. R. A. Idaboy, Computational Strategies for Predicting Free Radical Scavengers' Protection against Oxidative Stress: Where are we and What might Follow?, Int. J. Quantum Chem., Vol. 119, No. 2, 2019, pp. e25665, https://doi.org/10.1002/qua.25665.
[10] A. Galano, J. R. Alvarez‐Idaboy, A Computational Methodology for Accurate Predictions of Rate Constants in Solution: Application to the Assessment of Primary Antioxidant Activity, J. Comput. Chem., Vol. 34, No. 28, 2013, pp. 2430-2445, https://doi.org/10.1002/jcc.23409.
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https://doi.org/10.1039/D0NJ01567A.
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[17] K. U. Ingold, D. A. Pratt, Advances in Radical-Trapping Antioxidant Chemistry in the 21st Century: A Kinetics and Mechanisms Perspective, Chem. Rev., Vol. 114, No. 18, 2014, pp. 9022-9046, https://doi.org/10.1021/cr500226n.
[18] H. Boulebd, D. M. Pereira, I. A. Khodja, N. T. Hoa, A. Mechler, Q. V. Vo, Assessment of the Free Radical Scavenging Potential of Cannabidiol under Physiological Conditions: Theoretical and Experimental Investigations, J. Mol. Liq., Vol. 346, 2022, pp. 118277, https://doi.org/10.1016/j.molliq.2021.118277.
[19] Q. V. Vo, M. Van Bay, P. C. Nam, A. Mechler, Is Indolinonic Hydroxylamine a Promising Artificial Antioxidant?, J. Phys. Chem. B, Vol. 123, No. 37, 2019, pp. 7777-7784, https://doi.org/10.1021/acs.jpcb.9b05160.
[20] H. Zhou, X. Li, Y. Shang, K. Chen, Radical Scavenging Activity of Puerarin: A Theoretical Study, Antioxidants, Vol. 8, No. 12, 2019, pp. 590, https://doi.org/10.3390/antiox8120590.
[21] M. J. Li, L. Liu, Y. Fu, Q. X. Guo, Accurate Bond Dissociation Enthalpies of Popular Antioxidants Predicted by the Oniom-G3b3 Method, J. Mol. Struct. THEOCHEM, Vol. 815, No. 1-3, 2007, pp. 1-9,
https://doi.org/10.1016/j.theochem.2007.03.012.
[22] C. Iuga, J. R. A. Idaboy, A. V. Bunge, Ros Initiated Oxidation of Dopamine under Oxidative Stress Conditions in Aqueous and Lipidic Environments, J. Phys. Chem. B, Vol. 115, No. 42, 2011, pp. 12234-12246, https://doi.org/10.1021/jp206347u.
[23] Q. V. Vo, N. M. Thong, T. Le Huyen, P. C. Nam, N. M. Tam, N.T. Hoa, A. Mechler, A Thermodynamic and Kinetic Study of the Antioxidant Activity of Natural Hydroanthraquinones, RSC Adv., Vol. 10, No. 34, 2020, pp. 20089-20097, https://doi.org/10.1039/D0RA04013D.
[24] K. Chegaev, C. Cena, M. Giorgis, B. Rolando, P. Tosco, M. Bertinaria, R. Fruttero, P.-A. Carrupt, and A. Gasco, Edaravone Derivatives Containing No-Donor Functions, J. Med. Chem., Vol. 52, No. 2, 2009, pp. 574-578, https://doi.org/10.1021/jm8007008.
[25] C. Iuga, J. R. l. A. Idaboy, N. Russo, Antioxidant Activity of Trans-Resveratrol toward Hydroxyl and Hydroperoxyl Radicals: A Quantum Chemical and Computational Kinetics Study, J. Org. Chem., Vol. 77, No. 8, 2012, pp. 3868-3877, https://doi.org/10.1021/jo3002134.