Computational Study of The Effect of Structure on Antioxidant Activity and Drug Score of Coumarin Derivatives

Authors

  • Andi Budi Bakti Department of Chemistry, Institut Teknologi Bandung, Indonesia
  • Muhamad Abdulkadir Martoprawiro Department of Chemistry, Institut Teknologi Bandung, Indonesia

DOI:

https://doi.org/10.21580/wjc.v7i2.23327

Keywords:

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

Abstract

The presence of reactive oxygen species in the body must be maintained at low concentrations, as an excess can lead to oxidative stress. Coumarin, a secondary metabolite found in plants, exhibits potential as an antioxidant agent. However, the development of synthetic antioxidants based on coumarin remains limited. Computational studies enable the manipulation of coumarin structures to predict antioxidant activity. Correspondingly, this research aimed to investigate the effect of the type, number, and position of substituents on the antioxidant activity and drug score of coumarin derivatives utilizing computational methods, specifically ORCA and OSIRIS Property Explorer software. The results revealed that electron-donating substituents (e.g., OCH₃) could enhance antioxidant activity, while electron-withdrawing substituents (e.g., CHO) tended to reduce it. Substitution on the benzene ring of coumarin exerted a more significant effect on antioxidant activity compared to substitution on the pyrone ring. Compounds such as Umbelliferone, Scoparone, and 3-Bromoscoparone exhibited potential as new antioxidants due to their structural similarity to ascorbic acid or TBHQ. However, further studies are necessary to confirm their development as safe and effective antioxidants free from side effects.

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References

Donovalová, J., Cigáň, M., Stankovičová, H., Gašpar, J., Danko, M., Gáplovský, A., Hrdlovič, P., 2012. Spectral Properties of Substituted Coumarins in Solution and Polymer Matrices. Molecules 17, 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. Curr Pharm Des 10, 3813–33. https://doi.org/10.2174/1381612043382710

Gulcin, İ., 2020. Antioxidants and antioxidant methods: an updated overview. Arch Toxicol 94, 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. J Agric Food Chem 53, 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. Mol Divers. 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. J Am Chem Soc 124, 6421–6427. https://doi.org/10.1021/ja012474j

Lončar, M., Jakovljević, M., Šubarić, D., Pavlić, M., Buzjak Služek, V., Cindrić, I., Molnar, M., 2020. Coumarins in Food and Methods of Their Determination. Foods 9. 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. J Sci Food Agric 86, 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. Biochem Pharmacol 44, 205–14. 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. Oxid Med Cell Longev 2017, 8416763. https://doi.org/10.1155/2017/8416763

Wright, J.S., Johnson, E.R., DiLabio, G.A., 2001. Predicting the Activity of Phenolic Antioxidants: Theoretical Method, Analysis of Substituent Effects, and Application to Major Families of Antioxidants. J Am Chem Soc 123, 1173–1183. https://doi.org/10.1021/ja002455u

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, 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, 199–202. https://doi.org/10.1016/j.theochem.2003.12.014

Published

2024-12-31