Computational Study of the Influence of Structure on Antioxidant Activity and Drug Score of Coumarin Derivatives

Andi Budi Bakti, Muhamad Abdulkadir Martoprawiro

Abstract


The presence of reactive oxygen species (ROS) in the body must be maintained at low concentrations, excessive ROS and an inability to neutralize them can lead to oxidative stress. Coumarin, a secondary metabolite in plants, is used in pharmacology as an antioxidant agent. This study aims to identify the effects of the type, number, and position of substituents on coumarin derivatives's antioxidant activity and drug score using DFT methods. Computational tools, including ORCA software and OSIRIS Property Explorer, were employed. The results indicate that the number and position of electron-donating substituents, such as OCH3, enhance antioxidant activity, while electron-withdrawing substituents, like CHO, decrease it. Additionally, the presence of conjugated double bonds in the pyrone ring causes electron delocalization, complicating electron transfer. The compound 6,7-dimethoxyhydrocoumarin (hydroscoparone) shows potential as a new antioxidant due to its energy gap similar to commercial antioxidants like ascorbic acid and TBHQ, and a drug score of 0.5 with very low toxicity risk. However, further research is needed to confirm that this compound can be used as an effective antioxidant without side effects.


Keywords


antioxidant activity, coumarin derivates, computational method, drug score, OSIRIS

Full Text:

PDF

References


Donovalová, J., Cigáň, M., StankoviÄová, H., GaÅ¡par, J., Danko, M., Gáplovský, A., & HrdloviÄ, P. (2012). Spectral Properties of Substituted Coumarins in Solution and Polymer Matrices. Molecules, 17(3), 3259-3276. https://doi.org/10.3390/molecules17033259

Fylaktakidou, K. C., Hadjipavlou-Litina, D. J., Litinas, K. E., & Nicolaides, D. N. (2004). Natural and synthetic coumarin derivatives with anti-inflammatory/ antioxidant activities. Current Pharmaceutical Design, 10(30), 3813-3833. https://doi.org/10.2174/1381612043382710

Gulcin, Ä°. (2020). Antioxidants and antioxidant methods: an updated overview. Archives of Toxicology, 94(3), 651-715. https://doi.org/10.1007/s00204-020-02689-3

Huang, D., Ou, B., & Prior, R. L. (2005). The Chemistry behind Antioxidant Capacity Assays. Journal of Agricultural and Food Chemistry, 53(6), 1841-1856. https://doi.org/10.1021/jf030723c

Kumar, C., Chibber, P., Painuli, R., Haq, S. A., Vishwakarma, R. A., Singh, G., Satti, N. K., & Phatake, R. S. (2023). Scoparone chemical modification into semi-synthetic analogues featuring 3-substitution for their anti-inflammatory activity. Molecular Diversity. https://doi.org/10.1007/s11030-023-10687-7

Liptak, M. D., Gross, K. C., Seybold, P. G., Feldgus, S., & Shields, G. C. (2002). Absolute pKa Determinations for Substituted Phenols. Journal of the American Chemical Society, 124(22), 6421-6427. https://doi.org/10.1021/ja012474j

LonÄar, M., Jakovljević, M., Å ubarić, D., Pavlić, M., Buzjak Služek, V., Cindrić, I., & Molnar, M. (2020). Coumarins in Food and Methods of Their Determination. Foods (Basel, Switzerland), 9(5). https://doi.org/10.3390/foods9050645

MacDonald"Wicks, L. K., Wood, L. G., & Garg, M. L. (2006). Methodology for the determination of biological antioxidant capacity in vitro : a review. Journal of the Science of Food and Agriculture, 86(13), 2046-2056. https://doi.org/10.1002/jsfa.2603

Nakayama, T., & Uno, B. (2024). Electronic inductive and resonance effects of substituents on concerted two-proton-coupled electron transfer between electrogenerated superoxide and hydroquinone derivatives in N,N-dimethylformamide. Chemical Engineering Journal, 491, 152201. https://doi.org/10.1016/j.cej.2024.152201

Payá, M., Halliwell, B., & Hoult, J. R. (1992). Interactions of a series of coumarins with reactive oxygen species. Scavenging of superoxide, hypochlorous acid and hydroxyl radicals. Biochemical Pharmacology, 44(2), 205-214. https://doi.org/10.1016/0006-2952(92)90002-z

Pizzino, G., Irrera, N., Cucinotta, M., Pallio, G., Mannino, F., Arcoraci, V., Squadrito, F., Altavilla, D., & Bitto, A. (2017). Oxidative Stress: Harms and Benefits for Human Health. Oxidative Medicine and Cellular Longevity, 2017, 8416763. https://doi.org/10.1155/2017/8416763

Wulandari, A., Afrizal, A., Emriadi, E., Efdi, M., & Imelda, I. (2020). Studi komputasi terhadap struktur, sifat antioksidan, toksisitas dan skor obat dari scopoletin dan turunannya. CHEMPUBLISH JOURNAL, 5(1), 77-92. https://doi.org/10.22437/chp.v5i1.9023

Zhang, H.-Y., & Wang, L.-F. (2004). Theoretical elucidation of structure-activity relationship for coumarins to scavenge peroxyl radical. Journal of Molecular Structure: THEOCHEM, 673(1-3), 199-202. https://doi.org/10.1016/j.theochem.2003.12.014




DOI: https://doi.org/10.37905/jambchem.v7i2.27350

Refbacks

  • There are currently no refbacks.


Copyright (c) 2025 Jambura Journal of Chemistry



EDITORIAL OFFICE

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.