IN SILICO INVESTIGATION OF ANTIFUNGAL BIOACTIVE COMPOUNDS FROM Areca catechu SEEDS
INVESTIGASI IN SILICO SENYAWA BIOAKTIF ANTIJAMUR DARI BIJI PINANG (Areca catechu)
DOI:
https://doi.org/10.71275/roce.v3i2.222Keywords:
Areca catechu, antifungi, in silico, SwissADME, PKCSMAbstract
This study evaluated the antifungal potential of bioactive compounds present in betel nut seeds (Areca catechu L.) through an in silico approach. The assessment included prediction of antifungal activity (Pa), pharmacokinetic profiling using SwissADME, evaluation of physicochemical and drug-likeness properties, and toxicity prediction with pkCSM. The results indicated that betel nut seeds contain various bioactive constituents, including phenolic compounds, flavonoids, alkaloids, fatty acids, and proanthocyanidins, which may contribute to antifungal activity through different mechanisms. Among the analyzed compounds, proanthocyanidins showed the highest predicted antifungal activity, followed by arecoline and catechin. These compounds are expected to inhibit fungal growth by disrupting cell membrane integrity, reducing biofilm formation, and interfering with essential metabolic pathways. Pharmacokinetic analysis revealed that low-molecular-weight compounds, such as catechin, certain alkaloids, and fatty acids, generally exhibited greater solubility and drug-likeness, suggesting greater bioavailability. In contrast, larger polyphenolic compounds demonstrated lower absorption potential but may remain active through direct interactions with fungal cell surfaces. Toxicity predictions suggested that most compounds pose relatively low mutagenic risk, although some alkaloids may have hepatotoxic potential. Overall, the findings indicate that the antifungal properties of Areca catechu are likely attributable to the combined action of multiple bioactive compounds, highlighting its potential as a natural source for developing environmentally friendly antifungal agents.
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References
Ali, N. S., & Khuwaja, A. K. (2011). Chapter 23 - Betel Nut (Areca catechu) Usage and Its Effects on Health. In V. R. Preedy, R. R. Watson, & V. B. Patel (Eds.), Nuts and Seeds in Health and Disease Prevention (pp. 197–204). Academic Press. https://doi.org/https://doi.org/10.1016/B978-0-12-375688-6.10023-4
Bolton, E. E., Wang, Y., Thiessen, P. A., & Bryant, S. H. (2008). PubChem: Integrated Platform of Small Molecules and Biological Activities. Annual Reports in Computational Chemistry, 4, 217–241. https://api.semanticscholar.org/CorpusID:31561268
Daina, A., Michielin, O., & Zoete, V. (2017). SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Scientific Reports, 7(1), 42717. https://doi.org/10.1038/srep42717
El-Baky, N. A., & Amara, A. A. A. F. (2021). Recent Approaches towards Control of Fungal Diseases in Plants: An Updated Review. Journal of Fungi (Basel, Switzerland), 7(11). https://doi.org/10.3390/jof7110900
Fakhim, H., Mohamadi, B., Gharibi, S., Rahimmalek, M., Hosseini Rizi, M., Shelerangkon, M., Nasri, E., Dorostkar, F., Szumny, A., & Vaezi, A. (2025). Antifungal activity of polyphenolic compounds against fluconazole-susceptible and -resistant Candida species. Iranian Journal of Microbiology, 17(2), 342–347. https://doi.org/10.18502/ijm.v17i2.18398
Guimarães, A., & Venâncio, A. (2022). The Potential of Fatty Acids and Their Derivatives as Antifungal Agents: A Review. Toxins, 14(3). https://doi.org/10.3390/toxins14030188
Kang, X.-N., Tang, M.-M., Wu, M.-Z., Song, X.-M., Zhou, X.-M., & Ji, J.-B. (2026). Bioactive flavanes from the seeds of Areca catechu L. Natural Product Research, 1–6. https://doi.org/10.1080/14786419.2026.2615746
Khan, H., Mubarak, M. S., & Amin, S. (2017). Antifungal Potential of Alkaloids As An Emerging Therapeutic Target. Current Drug Targets, 18(16), 1825–1835. https://doi.org/10.2174/1389450117666160719095517
Khanzada, B., Akhtar, N., Okla, M. K., Alamri, S. A., Al-Hashimi, A., Baig, M. W., Rubnawaz, S., AbdElgawad, H., Hirad, A. H., Haq, I.-U., & Mirza, B. (2021). Profiling of Antifungal Activities and In Silico Studies of Natural Polyphenols from Some Plants. Molecules, 26(23). https://doi.org/10.3390/molecules26237164
Lai, J., Li, C., Zhang, Y., Wu, Z., Li, W., Zhang, Z., Ye, W., Guo, H., Wang, C., Long, T., Wang, S., & Yang, J. (2023). Integrated Transcriptomic and Metabolomic Analyses Reveal the Molecular and Metabolic Basis of Flavonoids in Areca catechu L. Journal of Agricultural and Food Chemistry, 71(12), 4851–4862. https://doi.org/10.1021/acs.jafc.2c08864
Leka, K., Mamede, L., Vandeberg, E., Garigliany, M.-M., & Ledoux, A. (2026). Natural Alkaloids as Antiviral Agents Against RNA Viruses: A Comprehensive and Mechanistic Review. Molecules (Basel, Switzerland), 31(3). https://doi.org/10.3390/molecules31030539
Liang, C., Gao, W., Ge, T., Tan, X., Wang, J., Liu, H., Wang, Y., Han, C., Xu, Q., & Wang, Q. (2021). Lauric Acid Is a Potent Biological Control Agent That Damages the Cell Membrane of Phytophthora sojae. Frontiers in Microbiology, Volume 12-2021. https://doi.org/10.3389/fmicb.2021.666761
Lin, X., Li, X., & Lin, X. (2020). A Review on Applications of Computational Methods in Drug Screening and Design. Molecules, 25(6). https://doi.org/10.3390/molecules25061375
Lindner, S., Keim, S., Haddadzadegan, S., Fernandez Romero, O., Zöller, K., Stern, G., Cesi, I., Kafedjiiski, K., & Bernkop-Schnürch, A. (2026). Strategies to Improve the Lipophilicity of Hydrophilic Macromolecular Drugs. Advanced Healthcare Materials, 15(5), e03721. https://doi.org/10.1002/adhm.202503721
Luiz, R. L. F., Vila, T. V. M., de Mello, J. C. P., Nakamura, C. V., Rozental, S., & Ishida, K. (2015). Proanthocyanidins polymeric tannin from Stryphnodendron adstringens are active against Candida albicans biofilms. BMC Complementary and Alternative Medicine, 15, 68. https://doi.org/10.1186/s12906-015-0597-4
Manach, C., Williamson, G., Morand, C., Scalbert, A., & Rémésy, C. (2005). Bioavailability and bioefficacy of polyphenols in humans. I. Review of 97 bioavailability studies. The American Journal of Clinical Nutrition, 81(1 Suppl), 230S-242S. https://doi.org/10.1093/ajcn/81.1.230S
Pires, D. E. V, Blundell, T. L., & Ascher, D. B. (2015). pkCSM: Predicting Small-Molecule Pharmacokinetic and Toxicity Properties Using Graph-Based Signatures. Journal of Medicinal Chemistry, 58(9), 4066–4072. https://doi.org/10.1021/acs.jmedchem.5b00104
Qiao, Y., Zhen, P., Gao, Q., Yu, F., Xie, Q., & Shi, J. (2026). Proanthocyanidins: structure, biosynthesis, regulation, and structure–activity relationships. ABIOTECH, 7(3), 100047. https://doi.org/https://doi.org/10.1016/j.abiote.2026.100047
Rauf, A., Imran, M., Abu-Izneid, T., Iahtisham-Ul-Haq, Patel, S., Pan, X., Naz, S., Sanches Silva, A., Saeed, F., & Rasul Suleria, H. A. (2019). Proanthocyanidins: A comprehensive review. Biomedicine & Pharmacotherapy, 116, 108999. https://doi.org/https://doi.org/10.1016/j.biopha.2019.108999
Sarma, A., Ramesha, N. K., Kumar, M., Udupa, S., Thorat, S. A., Kaniyassery, A., Naik, M. K., Chiang, Y.-C., & Muthusamy, A. (2026). Pharmacological and biological activities of areca nut (Areca catechu L.): A systematic review. Journal of Food Measurement and Characterization. https://doi.org/10.1007/s11694-026-04393-9
Selvaraj, S., Krishnaswamy, S., Devashya, V., Sethuraman, S., & Krishnan, U. M. (2015). Influence of membrane lipid composition on flavonoid–membrane interactions: Implications on their biological activity. Progress in Lipid Research, 58, 1–13. https://doi.org/https://doi.org/10.1016/j.plipres.2014.11.002
Shaker, B., Ahmad, S., Lee, J., Jung, C., & Na, D. (2021). In silico methods and tools for drug discovery. Computers in Biology and Medicine, 137, 104851. https://doi.org/https://doi.org/10.1016/j.compbiomed.2021.104851
Shearer, J., Castro, J. L., Lawson, A. D. G., MacCoss, M., & Taylor, R. D. (2022). Rings in Clinical Trials and Drugs: Present and Future. Journal of Medicinal Chemistry, 65(13), 8699–8712. https://doi.org/10.1021/acs.jmedchem.2c00473
Song, F., Tang, M., Wang, H., Zhang, Y., Zhu, K., Chen, X., Chen, H., & Zhao, X. (2022). UHPLC-MS/MS identification, quantification of flavonoid compounds from Areca catechu L. extracts and in vitro evaluation of antioxidant and key enzyme inhibition properties involved in hyperglycemia and hypertension. Industrial Crops and Products, 189, 115787. https://doi.org/https://doi.org/10.1016/j.indcrop.2022.115787
Sun, Y., Feng, J., Hou, W., Qi, H., & Liu, Y. (2024). Comprehensive insights into areca nut: active components and omics technologies for bioactivity evaluation and quality control. Frontiers in Pharmacology, Volume 15-2024. https://doi.org/10.3389/fphar.2024.1407212
Wang, R., Pan, F., He, R., Kuang, F., Wang, L., & Lin, X. (2021). Arecanut (Areca catechu L.) seed extracts extracted by conventional and eco-friendly solvents: Relation between phytochemical compositions and biological activities by multivariate analysis. Journal of Applied Research on Medicinal and Aromatic Plants, 25, 100336. https://doi.org/https://doi.org/10.1016/j.jarmap.2021.100336
Yan, Y., Li, X., Zhang, C., Lv, L., Gao, B., & Li, M. (2021). Research Progress on Antibacterial Activities and Mechanisms of Natural Alkaloids: A Review. Antibiotics, 10(3). https://doi.org/10.3390/antibiotics10030318
Yang, Z., Chen, K., Wang, Y., Li, J., He, Y., Zhuang, J., & Qi, J. (2026). From permeability to prediction: evolving strategies for evaluating oral drug absorption. International Journal of Pharmaceutics, 694, 126725. https://doi.org/10.1016/j.ijpharm.2026.126725
Zouine, N., Ghachtouli, N. El, Abed, S. El, & Koraichi, S. I. (2024). A comprehensive review on medicinal plant extracts as antibacterial agents: Factors, mechanism insights and future prospects. Scientific African, 26, e02395.https://doi.org/https://doi.org/10.1016/j.sciaf.2024.e02395
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Copyright (c) 2026 Erwan, Egi Saputra, Deky Alfiansyah, Muhammad Farell Islami Pasha, Julianti, Iqlima Nadya Putri, Dodi Iskandar, Dimas Fitra Miardhan (Author)
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