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A Quantum Chemical Study on the Antioxidant Properties of Myricetin, Quercetin, and Kaempferol Using Density Functional Theory (DFT) and Molecular Docking

Year 2024, Volume: 45 Issue: 4, 740 - 749, 30.12.2024

Mustafa Elik

https://doi.org/10.17776/csj.1513540

Abstract

This study explores the antioxidant properties of myricetin, quercetin, and kaempferol using density functional theory (DFT) and molecular docking analyses. The findings of this study not only highlight the significant antioxidant potential of flavonoids and provide a foundation for potential clinical applications and future research aimed at optimizing their pharmacokinetic properties for therapeutic use. The optimized geometries of these flavonoids were determined through DFT calculations at the B3LYP/6-31G(d,p) level. Key electronic properties, such as total electronic energy (Eₜ), zero-point energy (ZPE), enthalpy (H), entropy (S), dipole moment (μ), and HOMO-LUMO energy gaps (ΔE_H-L), were computed to evaluate molecular stability and reactivity. Molecular docking with proteins 1HD2, 1RAU, 3FZS, and 3GRS revealed strong binding affinities, particularly for myricetin, which achieved docking scores of -5.330 with 1HD2 and -8.652 with 3GRS, indicating a high potential for antioxidant activity. ADME analyses demonstrated that kaempferol exhibited the most favorable pharmacokinetic profile, with a human oral absorption rate of 63.637% and compliance with Lipinski’s Rule of Five. Conversely, myricetin showed reduced bioavailability despite its strong binding affinity. This work emphasizes optimizing flavonoid pharmacokinetics to maximize their therapeutic potential while reinforcing their relevance in antioxidant therapy.

Keywords

Antioxidant activity Density functional theory (DFT) Molecular docking Flavonoids and pharmacokinetics (ADME

References

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Year 2024, Volume: 45 Issue: 4, 740 - 749, 30.12.2024

Mustafa Elik

https://doi.org/10.17776/csj.1513540

Abstract

References

  • [1] Mohamed N., Effect of antioxidants in promoting plant growth under climate change conditions, Research on Crops, 21 (2) (2020) 424-434.
  • [2] Agrimonti C., Lauro M., Visioli G., Smart agriculture for food quality: Facing climate change in the 21st century, Crit. Rev. Food Sci. Nutr., 61 (6) (2021) 971-981.
  • [3] Orona-Tamayo D., Paredes-López O., Chia—The new golden seed for the 21st century: Nutraceutical properties and technological uses, Sustainable Protein Sources, Academic Press, (2024) 443-470.
  • [4] Bir A., Ghosh A., Chauhan A., Saha S., Saini A. K., Bisaglia, M., Chakrabarti, S., Exosomal Dynamics and Brain Redox Imbalance: Implications in Alzheimer’s Disease Pathology and Diagnosis, Antioxidants, 13 (3) (2024) 316.
  • [5] Tumilaar S. G., Hardianto A., Dohi H., Kurnia D., A Comprehensive Review of Free Radicals, Oxidative Stress, and Antioxidants: Overview, Clinical Applications, Global Perspectives, Future Directions, and Mechanisms of Antioxidant Activity of Flavonoid Compounds, J. Chem., 2024 (1) (2024) 5594386.
  • [6] Caiati C., Stanca A., Lepera M. E., Free radicals and obesity-related chronic inflammation contrasted by antioxidants: A new perspective in coronary artery disease, Metabolites, 13 (6) (2023) 712.
  • [7] Pruteanu L. L., Bailey D. S., Grădinaru A. C., Jäntschi L., Pammi S. S., Suresh B., Giri A., The biochemistry and effectiveness of antioxidants in food, fruits, and marine algae, Antioxidants, 12 (4) (2023) 860.
  • [8] Sen S., Chakraborty R., Sridhar C., Reddy Y. S. R., De B., Free radicals, antioxidants, diseases and phytomedicines: current status and future prospect, Int J Pharm Sci Rev Res, 3 (1) (2010) 91-100.
  • [9] Andrés C. M. C., Pérez de la Lastra J. M., Bustamante Munguira E., Juan C. A., Plou F. J., Pérez Lebeña E., Electrophilic Compounds in the Human Diet and Their Role in the Induction of the Transcription Factor NRF2, Int. J. Mol. Sci., 25 (6) (2024) 3521.
  • [10] Daniloski D., Petkoska A. T., Lee N. A., Bekhit A. E. D., Carne A., Vaskoska, R., Vasiljevic, T., Active edible packaging based on milk proteins: A route to carry and deliver nutraceuticals, Trends Food Sci. Technol., 111 (2021) 688-705.
  • [11] Ayoka T. O., Ezema B. O., Eze C. N., Nnadi C. O., Antioxidants for the Prevention and Treatment of Non-communicable Diseases, J. Explor. Res. Pharmacol., 7 (3) (2022) 179-189.
  • [12] Di Meo S., Venditti P., Evolution of the knowledge of free radicals and other oxidants, Oxid. Med. Cell. Longev., 2020 (1) (2020) 9829176.
  • [13] Engwa G. A., Nweke F. N., Nkeh-Chungag B. N., Free radicals, oxidative stress-related diseases and antioxidant supplementation, Altern. Ther. Health Med., 28 (1) (2022).
  • [14] Wang W., Kang P. M., Oxidative stress and antioxidant treatments in cardiovascular diseases, Antioxidants, 9 (12) (2020) 1292.
  • [15] Dubois-Deruy E., Peugnet V., Turkieh A., Pinet F., Oxidative stress in cardiovascular diseases, Antioxidants, 9 (9) (2020) 864.
  • [16] Saini N., Kataria R., Bhardwaj I., Panchal P., Importance of Flavonoids in Agriculture, Flavonoids as Nutraceuticals, Apple Academic Press, (2024) 37-55.
  • [17] Yan Q., Liu S., Sun Y., Chen C., Yang S., Lin M., Yang Y., Targeting oxidative stress as a preventive and therapeutic approach for cardiovascular disease, J. Transl. Med., 21 (1) (2023) 519.
  • [18] Zandavar H., Babazad M. A., Secondary metabolites: Alkaloids and flavonoids in medicinal plants, Herbs and Spices-New Advances, IntechOpen, (2023).
  • [19] Pietta P. G., Flavonoids as antioxidants, J. Nat. Prod., 63 (7) (2000) 1035-1042.
  • [20] Ma P., Wang Z., Density Functional Theory Study on Antioxidant Activity of Three Polyphenols, J. Fluoresc., 33 (3) (2023) 933-944.
  • [21] Sun C., Cao B., Yin H., Shi Y., Relationship between ESIPT properties and antioxidant activities of 5-hydroxyflavone derivates, Chin. Phys. B, 29(5) (2020) 058202.
  • [22] Frisch M. J., Trucks G. W., Schlegel 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, Revision C.02, Gaussian, Inc., Wallingford CT, 2004.
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  • [24] Schrödinger Release 2024-2: Maestro, Schrödinger, LLC, New York, NY, 2024.
  • [25] de Lima, D. P., Júnior, E. D. S. P., de Menezes, A. V., de Souza, D. A., de São José, V. P. B., da Silva, B. P., ... & de Carvalho, I. M. M., Chemical composition, minerals concentration, total phenolic compounds, flavonoids content and antioxidant capacity in organic and conventional vegetables, Food Research International, 175 (2024) 113684.
  • [26] Indiarto, R., Herwanto, J. A., Filianty, F., Lembong, E., Subroto, E., Muhammad, D. R. A., Total phenolic and flavonoid content, antioxidant activity and characteristics of a chocolate beverage incorporated with encapsulated clove bud extract, CyTA-Journal of Food, 22(1) (2024) 2329144.
  • [27] Schrödinger Release 2024-2: LigPrep, Schrödinger, LLC, New York, NY, 2024.
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  • [29] Glevitzky I., Dumitrel G. A., Glevitzky M., Pasca B., Otrisal P., Bungau S., Popa, M. J. R. C., Statistical analysis of the relationship between antioxidant activity and the structure of flavonoid compounds, Rev. Chim, 70(9) (2019) 3103-3107.
  • [30] Wang R., Li W., Fang C., Zheng X., Liu C., Huang Q., Extraction and identification of new flavonoid compounds in dandelion Taraxacum mongolicum Hand.-Mazz. with evaluation of antioxidant activities, Scientific Reports, 13(1) (2023) 2166.
  • [31] Wang Y., Li C., Li Z., Moalin M., Hartog G. J. D., Zhang M., Computational Chemistry Strategies to Investigate the Antioxidant Activity of Flavonoids An Overview, Molecules, 29(11) (2024) 2627.
  • [32] Miličević A., Flavonoid Oxidation Potentials and Antioxidant Activities-Theoretical Models Based on Oxidation Mechanisms and Related Changes in Electronic Structure, International Journal of Molecular Sciences, 25(9) (2024) 5011.
  • [33] Monzani E., Koolhaas G.A.A., Spandre A., Leggieri E., Casella L., Gullotti M., Reedijk J., Binding of nitrite and its reductive activation to nitric oxide at biomimetic copper centers, JBIC Journal of Biological Inorganic Chemistry, 5 (2000) 251-261.
  • [34] Jovanovic S. V., Steenken S., Tosic M., Marjanovic B., Simic M.G., Flavonoids as antioxidants, J. Am. Chem. Soc., 116(11) (1994) 4846-4851.
  • [35] Mejía J. J., Sierra L. J., Ceballos J. G., Martínez J. R., Stashenko E.E., Color, antioxidant capacity and flavonoid composition in Hibiscus rosa-sinensis cultivars, Molecules, 28(4) (2023) 1779.
  • [36] Utami Y.P., Yulianty R., Djabir Y.Y., Alam G., Antioxidant Activity, Total Phenolic and Total Flavonoid Contents of Etlingera elatior (Jack) RM Smith from North Luwu, Indonesia, Tropical Journal of Natural Product Research, 8(1) (2024).
There are 36 citations in total.

Details

Primary Language English
Subjects Physical Organic Chemistry, Free Radical Chemistry, Computational Chemistry
Journal Section Natural Sciences
Authors

Mustafa Elik 0000-0001-8245-4273

Publication Date December 30, 2024
Submission Date July 9, 2024
Acceptance Date December 11, 2024
Published in Issue Year 2024Volume: 45 Issue: 4

Cite

APA Elik, M. (2024). A Quantum Chemical Study on the Antioxidant Properties of Myricetin, Quercetin, and Kaempferol Using Density Functional Theory (DFT) and Molecular Docking. Cumhuriyet Science Journal, 45(4), 740-749. https://doi.org/10.17776/csj.1513540
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