Prediction of compounds from breadfruit plants (Artocarpus altilis) as alpha estrogen receptor agonists for novel breast cancer anticancer therapy: an in silico approach
https://doi.org/10.21294/1814-4861-2025-24-2-68-78
Abstract
The aim of this study was to investigate the potential of compounds from the breadfruit tree (Artocarpus altilis) as anti-breast cancer agents using in silico techniques. Material and Methods. The methods used in this study include molecular docking and ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) predictions to evaluate the interactions with Estrogen Receptor alpha (ERα). Results. Among the 22 compounds tested, Cycloaltisin-7 exhibited the most favorable binding affinity, with a free energy of -10.25 kcal/ mol and an inhibition constant of 30.89 nM. Additionally, Cyclocommunol and Cudraflavone B demonstrated significant binding interactions, with free energies of -9.61 kcal/mol and -9.53 kcal/mol, and inhibition constants of 90.82 nM and 103.50 nM, respectively. For comparison, the standard compound 4-Hydroxytamoxifen showed superior binding characteristics, with a free energy of -12.36 kcal/mol and an inhibition constant of 867.83 pM. ADMET predictions indicate that Cycloaltisin-7, Cyclocommunol, and Cudraflavone B meet essential drug-like criteria, suggesting their potential as viable candidates for further development as breast cancer therapeutics. Conclusion. These findings highlight Cycloaltisin-7 as a particularly promising compound, with Cyclocommunol and Cudraflavone B also showing considerable potential. This research provides valuable insights for the advancement of plant-based treatments for breast cancer.
Supporting agencies: This study was funded by APBU 2024 Research Grant Universitas Islam Kalimantan MAB Banjarmasin, Indonesia.
About the Authors
N. Su’aida
Faculty of Pharmacy, Universitas Islam Kalimantan Muhammad Arsyad Al Banjari Banjarmasin
Indonesia
Indonesia
Nily Su’aida, Assistant Professor, Pharmacy Department, Faculty of Pharmacy
Author ID (Scopus): 58030395300
South Kalimantan, Banjarmasin, 70234
R. R. Pratama
Faculty of Pharmacy, Universitas Islam Kalimantan Muhammad Arsyad Al Banjari Banjarmasin
Indonesia
Indonesia
Rizki Rahmadi Pratama, Assistant Professor, Pharmacy Department, Faculty of Pharmacy
Author ID (Scopus): 58110640100
South Kalimantan, Banjarmasin, 70234
A. Fadillah
Faculty of Pharmacy, Universitas Islam Kalimantan Muhammad Arsyad Al Banjari Banjarmasin
Indonesia
Indonesia
Aris Fadillah, Assistant Professor, Pharmacy Department, Faculty of Pharmacy
Author ID (Scopus): 57339399900
South Kalimantan, Banjarmasin, 70234
M. Fauzi
Faculty of Pharmacy, Universitas Islam Kalimantan Muhammad Arsyad Al Banjari Banjarmasin
Indonesia
Indonesia
Muhammad Fauzi, Assistant Professor, Pharmacy Department, Faculty of Pharmacy
Author ID (Scopus): 57218821752
South Kalimantan, Banjarmasin, 70234
References
1. Canter P.H., Thomas H., Ernst E. Bringing medicinal plants into cultivation: opportunities and challenges for biotechnology. Trends Biotechnol. 2005; 23(4): 180–85. doi: 10.1016/j.tibtech.2005.02.002.
2. Chaachouay N., Zidane L. Plant-derived natural products: A source for drug discovery and development. Drugs Drug Candidates. 2024; 3(1): 184–207. https://doi.org/10.3390/ddc3010011.
3. Sung H., Ferlay J., Siegel R.L., Laversanne M., Soerjomataram I., Jemal A., Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021; 71(3): 209–49. doi: 10.3322/caac.21660.
4. Ferlay J., Ervik M., Lam F., Colombet M., Mery L., Piñeros M., Znaor A., Soerjomataram I., Bray F. Global Cancer Obser-Vatory: Cancer Today. International Agency for Research on Cancer. France: Lyon, 2020. [cited 2024 Mar 3]. URL: https://gco.iarc.fr/today.
5. Appiah F., Oduro I.N., Ellis W.O. Proximate and Mineral Composition of Artocarpus altilis Pulp Flour as Affected by Fermentation. Pakistan Journal of Nutrition. 2011; 10(7): 653–57. doi: 10.3923/pjn.2011.653.657.
6. Arung E.T., Wicaksono B.D., Handoko Y.A., Kusuma I.W., Yulia D., Sandra F. Anticancer properties of diethylether extract of wood from sukun (Artocarpus altilis) in human breast cancer (T47D) cells. Tropical Journal of Pharmaceutical Research. 2009; 8(4): 317–24.
7. Boonphong S., Baramee A., Kittakoop P., Puangsombat P. Antitubercular and Antiplasmodial Prenylated Flavones from the Roots of Artocarpus altilis. Chiang Mai J. Sci. 2007; 34(3): 339–44.
8. Lan W.C., Tzeng C.W., Lin C.C., Yen F.L., Ko H.H. Prenylated flavonoids from Artocarpus altilis: antioxidant activities and inhibitory effects on melanin production. Phytochemistry. 2013; 89: 78–88. doi: 10.1016/j.phytochem.2013.01.011.
9. Khan M.R., Omoloso A.D., Kihara M. Antibacterial activity of Artocarpus heterophyllus. Fitoterapia. 2003; 74(5): 501–5. doi: 10.1016/s0367-326x(03)00120-5.
10. Weng J.R., Chan S.C., Lu Y.H., Lin H.C., Ko H.H., Lin C.N. Antiplatelet prenylflavonoids from Artocarpus communis. Phytochemistry. 2006; 67(8): 824–29. doi: 10.1016/j.phytochem.2006.01.030.
11. Jayasinghe L., Balasooriya B.A., Padmini W.C., Hara N., Fujimoto Y. Geranyl chalcone derivatives with antifungal and radical scavenging properties from the leaves of Artocarpus nobilis. Phytochemistry. 2004; 65(9): 1287–90. doi: 10.1016/j.phytochem.2004.03.033.
12. Widyawaruyanti A., Subehan, Kalauni S.K., Awale S., Nindatu M., Zaini N.C., Syafruddin D., Asih P.B.S., Tezuka Y., Kadota S. New prenylated flavones from Artocarpus champeden, and their antimalarial activity in vitro. J Nat Med. 2007; 61: 410–13. doi: 10.1007/s11418-007-0153-8.
13. Ko H.H., Lu Y.H., Yang S.Z., Won S.J., Lin C.N. Cytotoxic prenylflavonoids from Artocarpus elasticus. J Nat Prod. 2005; 68(11): 1692–95. doi: 10.1021/np050287j.
14. Fauzi M., Fadillah A., Rahman F., Ramadhani J., Erlianti K., Hasniah, Soemarie Y.B., Malik A. Activity Screening and Structure Modification of Artocarpin Against Ace2 and Main Protease Through In Silico Method. Int J App Pharm. 2021; 13(6): 192–98. doi: 10.22159/ijap.2021v13i6.42571.
15. Sommer S., Fuqua S.A. Estrogen receptor and breast cancer. Semin Cancer Biol. 2001; 11(5): 339–52. doi: 10.1006/scbi.2001.0389.
16. Yaşar P., Ayaz G., User S.D., Güpür G., Muyan M. Molecular mechanism of estrogen-estrogen receptor signaling. Reprod Med Biol. 2016; 16(1): 4–20. doi: 10.1002/rmb2.12006.
17. Ali S., Coombes R.C. Estrogen receptor alpha in human breast cancer: occurrence and significance. J Mammary Gland Biol Neoplasia. 2000; 5(3): 271–81. doi: 10.1023/a:1009594727358.
18. Carausu M., Bidard F.C., Callens C., Melaabi S., Jeannot E., Pierga J.Y., Cabel L. ESR1 mutations: a new biomarker in breast cancer. Expert Rev Mol Diagn. 2019; 19(7): 599–611. doi: 10.1080/14737159.2019.1631799.
19. Liang Y., Zhang H., Song X., Yang Q. Metastatic heterogeneity of breast cancer: Molecular mechanism and potential therapeutic targets. Semin Cancer Biol. 2020; 60: 14–27. doi: 10.1016/j.semcancer.2019.08.012.
20. Fauzi M., Saptarini N.M., Mustarichie R. In silico-screening of compounds contained in wera (Malvaviscus arboreus cav.) leaves as anti-alopecia with androgen receptors. J Glob Pharma Technol. 2019; 11(6): 309–17.
21. Fauzi M., Muchtaridi M. Synthesis and Anti-Breast Cancer Activities of Alpha Mangostin Derivatives: A Review. Rasayan J Chem. 2020; 13(4): 2544–51. doi: 10.31788/RJC.2020.1345769.
22. Arwansyah Ambarsari L., Sumaryada T.I. Simulasi Docking senyawa kurkumin dan analognya sebagai inhibitor reseptor androgen pada kanker prostat. Current Biochemistry. 2014; 1(1): 11–19.
23. Pandey A.K., Verma S. An in-silico evaluation of dietary components for structural inhibition of SARS-Cov-2 main protease. J Biomol Struct Dyn. 2020; 1–7. doi: 10.1080/07391102.2020.1809522.
24. Suwardi Salin A., Mahendra J.A.Y., Wijayanto D.B.A., Rochiman N.A., Anam S.K., Hikmah N. Virtual Screening, Pharmacokinetic Prediction, Molecular Docking and Dynamics Approaches in the Search for Selective and Potent Natural Molecular Inhibitors of MAO-B for the Treatment of Neurodegenerative Diseases. Indonesiam Journal of Chemistry and Environment. 2023; 6(2): 95–110.
25. Haddad M.J., Sztupecki W., Delayre-Orthez C., Rhazi L., Barbezier N., Depeint F., Anton P.M. Complexification of In Vitro Models of Intestinal Barriers, A True Challenge for a More Accurate Alternative Approach. Int J Mol Sci. 2023; 24(4): 3595. doi: 10.3390/ijms24043595.
26. Ahmad I., Kuznetsov A.E., Pirzada A.S., Alsharif K.F., Daglia M., Khan H. Computational pharmacology and computational chemistry of 4-hydroxyisoleucine: Physicochemical, pharmacokinetic, and DFT-based approaches. Front Chem. 2023; 11. doi: 10.3389/fchem.2023.1145974.
27. Pecoraro B., Tutone M., Hoffman E., Hutter V., Almerico A.M., Traynor M. Predicting Skin Permeability by Means of Computational Approaches: Reliability and Caveats in Pharmaceutical Studies. J Chem Inf Model. 2019; 59(5): 1759–71. doi: 10.1021/acs.jcim.8b00934.
28. Yates J.W., Arundel P.A. On the volume of distribution at steady state and its relationship with two-compartmental models. J Pharm Sci. 2008; 97(1): 111–22. doi: 10.1002/jps.21089.
29. Alajangi H.K., Kaur M., Sharma A., Rana S., Thakur S., Chatterjee M., Singla N., Jaiswal P.K., Singh G., Barnwal R.P. Blood-brain barrier: emerging trends on transport models and new-age strategies for therapeutics intervention against neurological disorders. Mol Brain. 2022; 15(1): 49. doi: 10.1186/s13041-022-00937-4.
30. Zeiadeh I., Najjar A., Karaman R. Strategies for Enhancing the Permeation of CNS-Active Drugs through the Blood-Brain Barrier: A Review. Molecules. 2018; 23(6). doi: 10.3390/molecules23061289.
31. Garza A.Z., Park S.B., Kocz R. Drug Elimination. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing, 2024. [cited 2023 Jul 4]. URL: https://www.ncbi.nlm.nih.gov/books/NBK547662/.
32. Chevret S. Maximum Tolerable Dose (MTD). Wiley StatsRef: Statistics Reference Online. 2014. https://doi.org/10.1002/9781118445112.stat07089.
33. Gulati K., Reshi M.R., Rai N., Ray A. Hepatotoxicity: Its Mechanisms, Experimental Evaluation and Protective Strategies. Am J Pharmacol. 2018; 1(1).
Review
For citations:
Su’aida N., Pratama R., Fadillah A., Fauzi M. Prediction of compounds from breadfruit plants (Artocarpus altilis) as alpha estrogen receptor agonists for novel breast cancer anticancer therapy: an in silico approach. Siberian journal of oncology. 2025;24(2):68-78. https://doi.org/10.21294/1814-4861-2025-24-2-68-78
Views:
860
Email this article 
