IN SILICO STUDY OF SOYBEAN (Glycine max L.) ISOFLAVONES FOR ANTI-BREAST CANCER THROUGH HER2 TARGETING
DOI:
https://doi.org/10.36858/ipj.v2i2.45Keywords:
Breast cancer, HER2, Isoflavones, in silicoAbstract
One of the cancers with the most excellent death rates worldwide, including in Indonesia, is breast cancer. Elevated HER2 expression significantly contributes to breast cancer progression by stimulating cell proliferation. Targeted therapies such as trastuzumab have limitations due to potential side effects. This study aims to identify the possible role of soybean (Glycine max L.) isoflavone compounds in inhibiting HER2 using an in silico approach prediction of physicochemical properties, pharmacokinetics, and bioactivity through SwissADME and PASS Online. The Hex 8.0.0 docking tool and Biovia Discovery Studio 2019 looked into how molecules interact with each other in complicated ways. Our study revealed that physicochemically the compounds acetylgenistin, acetylglycitin, and acetyldaidzin met Lipinski's Rule of Five criteria (BM (< 500), Log P (< 5), HBD (< 5), HBA (< 10), and MR (40-130)), pharmacokinetically the compound acetylgenistin met the ADME parameters and bioactively all six compounds had anticancer activity (Pa > 0.2). Based on the results of molecular docking analysis, the six soy isoflavone compounds can interact and have low binding energy values. The binding energy values of malonylgenistin, acetylgenistin, and acetyldaidzin are the lowest and close to trastuzumab, at -286.6, -283.4, and -277.7kcal/mol, respectively. These findings suggest that soybean (Glycine max L.) isoflavone compounds have potential as anticancer drug candidates in inhibiting HER2.
References
Abdulkadir, W. S., Puana, F., Taupik, M., Tungadi, R., Hutuba, A. H., Nurrohwinta, E., Ramahdani, F. N., & Hiola, F. (2024). Original Research Article In Silico Analysis of Isoflavone Compounds in Soybean (Glycine max L) as Anti-Breast Cancer Agents Targeting Estrogen Receptor Alpha. Tropical Journal of Phytochemistry & Pharmaceutical Sciences, 3(7).
Aertgeerts, K., Skene, R., Yano, J., Sang, B.-C., Zou, H., Snell, G., Jennings, A., Iwamoto, K., Habuka, N., Hirokawa, A., Ishikawa, T., Tanaka, T., Miki, H., Ohta, Y., & Sogabe, S. (2011). Structural Analysis of the Mechanism of Inhibition and Allosteric Activation of the Kinase Domain of HER2 Protein. Journal of Biological Chemistry,286 (21), 18756-18765. https://doi.org/10.1074/jbc.M110,206193
Agustin, A. T., Julianto, E., Julianus, J., & Riranto, J. (2022). Potential Role of Betel Leaf (Piper betle L.) Water Extract as Antibacterial Escherichia coli Through Inhibition of β-Ketoacyl-[Acyl Carrier Protein] Synthase I. Tropical Journal of Natural Product Research,6 (11), 1802-1808. https://doi.org/10,26538/tjnpr/v6i11.10
Astuty, P., & Komari, N. (2022). Molecular Docking Study of Karwinaphthol B Compound from Dayak Onion Plant (Eleutherine palmifolia (L.) Merr) as Glucokinase Enzyme Inhibitor. Journal of Natural Scientiae,2 (1). https://doi.org/10,20527/jns.v2i1.5412
Bray, F., Laversanne, M., Sung, H., Ferlay, J., Siegel, R. L., Soerjomataram, I., & Jemal, A. (2024). Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer Journal for Clinicians,74 (3), 229-263. https://doi.org/10.3322/caac.21834
Cahyani, N. K. N., Putri, W. N. E., Dwivayana, I. K. D., Mirayanti, N. P. D., & Laksmiani, N. P. L. (2021). In silico study of lutein as anti-HER-2 receptors in breast cancer treatment. Pharmacy Reports,1 (1), 17. https://doi.org/10.51511/pr.17
Kartika, W. A. (2024). a Molecular Docking of Meniran (Phyllanthus niruri L.) Against Tyrosine Kinase Enzyme Inhibition as Anticancer: Molecular Docking. Indonesian Journal of Pharmaceutical and Clinical Research,7 (2), 14-24. https://doi.org/10.32734/idjpcr.v7i2.17993
Khaerunnisa, A. B., Latief, S., Syahruddin, F. I., Royani, I., & Juhamran, R. P. (2023). Relationship between Knowledge Level and Attitude towards Early Detection of Breast Cancer in Employees of Ibnu Sina Hospital Makassar. Fakumi Medical Journal.
Komari, N., Adawiyah, R., Suhartono, E., & Hadi, S. (2022). Interaction of Gallic Acid and Methyl Galate from Kasturi Plant (Mangifera casturi) as Human Epidermal Growth Factor 2 (HER- 2) Protein Inhibitor: Molecular Docking Evaluation. 15.
Lee, Y. H., Kim, B., Hwang, S.-R., Kim, K., & Lee, J. H. (2018). Rapid characterization of metabolites in soybean using ultra high performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry (UPLC-ESI-Q-TOF-MS/MS) and screening for α-glucosidase inhibitory and antioxidant properties through different solvent systems. Journal of Food and Drug Analysis,26 (1), 277-291. https://doi.org/10.1016/j.jfda.2017.05.005
Maadi, H., Soheilifar, M. H., Choi, W.-S., Moshtaghian, A., & Wang, Z. (2021). Trastuzumab Mechanism of Action; 20 Years of Research to Unravel a Dilemma. Cancers,13 (14), 3540. https://doi.org/10.3390/cancers13143540
Maulana, A. M., Kusmardi, K., Purwaningsih, E. H., Hestiantoro, A., Mahmud, T., Wibowo, H., Priosoeryanto, B. P., Rustamadji, P., & Rusdi, N. K. (2024). Inhibitory Mechanisms of Soybean Extract on the Development of Breast Cancer Through Modulation of Cellular Immune Response. Pharmacognosy Journal,16 (1), 01-08. https://doi.org/10.5530/pj.2024.16.1
Mutiah, R., Dewi, T. J. D., Suryadinata, A., & Qonita, K. (2021). Inhibition of Human Epidermal Growth Factor Receptor-2 (HER-2) from Pomelo (Citrus maxima) Flavonoid Compounds: An In Silico Approach. Indonesian Journal of Cancer Chemoprevention,12 (3), 148. https://doi.org/10.14499/indonesianjcanchemoprev12iss3pp148-160
Novianty, R. (2023). Analysis of the interaction of guvacolin and homoarecolin compounds against MAO-A in silico. Photon: Journal of Science and Health,13 (1). https://doi.org/10.37859/jp.v13i1.5042
Pejčić, T., Zeković, M., Bumbaširević, U., Kalaba, M., Vovk, I., Bensa, M., Popović, L., & Tešić, Ž. (2023). The Role of Isoflavones in the Prevention of Breast Cancer and Prostate Cancer. Antioxidants,12 (2), 368. https://doi.org/10.3390/antiox12020368
Pratama, F., Ruswanto, R., Nofianti, T., Pratita, A. T. K., Daruwati, I., Susilo, V. Y., & Holik, H. A. (2024). Radiolabeling and In-Silico Study of 131I-(4-fluorobenzoyl-3-methylthiourea) as Radiopharmaceuticals for Breast Cancer Theranostics. Journal of Valence Chemistry,10 (1), 27-44. https://doi.org/10.15408/jkv.v10i1.34258
Rizka, A., Akbar, M. K., & Putri, N. A. (2022). Carcinoma Mammae Sinistra T4bn2m1 Metastasis Pleura. Averrous: Malikussaleh Journal of Medicine and Health,8 (1), 23. https://doi.org/10,29103/averrous.v8i1.7006
Suhandi, C. (2021). Review: Epidermal Growth Factor Receptor Targeted Drug Delivery System in Breast Cancer. Pharmaceutics Magazine,6 (4), 344. https://doi.org/10,24198/mfarmasetika.v6i4.35699
Ton Tai, D. X., Huong, L. T., Mai, T. H., Hung, V. M., Huyen, N. T., & Tung, B. T. (2023). Screening in silico the human epidermal growth factor receptor-2inhibitory effect of isoflavones by molecular docking method for their potential use in breast cancer. Ministry of Science and Technology, Vietnam,65 (2), 47-53. https://doi.org/10.31276/VJSTE.65(2).47-53
Tribudi, Y. A., Agustin, A. T., Setyaningtyas, D. E., & Gusmalawati, D. (2022). Bioactive Compound Profile and Biological Modeling Reveals the Potential Role of Purified Methanolic Extract of Sweet Flag (Acorus calamus L.) in Inhibiting the Dengue Virus (DENV) NS3 Protease-Helicase. Indonesian Journal of Chemistry,22 (2), 331-341. https://doi.org/10,22146/ijc.68317
Zhu, K., Yang, X., Tai, H., Zhong, X., Luo, T., & Zheng, H. (2024). HER2-targeted therapies in cancer: A systematic review. Biomarker Research,12 (1), 16. https://doi.org/10.1186/s40364-024-00565-1
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2025 Ayu Tri Agustin, Nadia Khairun Nisa, IGA Karnasih, Mohammad Rofik Usman, Shinta Mayasari
This work is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.
