In Silico Evaluation of Bisbenzylisoquinoline Compounds from Stephania sp. as EGFR Inhibitors for Triple-Negative Breast Cancer

Amanda Triastuti Amanda; Denny Satria

doi:10.24036/eksakta/vol27-iss02/677

EKSAKTA: Berkala Ilmiah Bidang MIPA

Open Access

In Silico Evaluation of Bisbenzylisoquinoline Compounds from Stephania sp. as EGFR Inhibitors for Triple-Negative Breast Cancer

Amanda Triastuti Amanda ¹

, Denny Satria ¹

¹ Department of Pharmaceutical Biology, Faculty of Pharmacy, Universitas Sumatera Utara, Medan, Indonesia

Published 2026-04-30

Vol. 27 No. 02 (2026) PAGES 231-240

DOI 10.24036/eksakta/vol27-iss02/677

Views / Downloads 20 30

Download PDF

Abstract

Triple-negative breast cancer (TNBC) represents a highly aggressive breast malignancy subtype characterized by constrained therapeutic alternatives and poor clinical outcomes. Since Epidermal Growth Factor Receptor (EGFR) is frequently overexpressed in TNBC, it remains a strategic molecular target for anticancer drug innovation. This study evaluates the inhibitory potential of bisbenzylisoquinoline (BBIQ) compounds from Stephania species against EGFR using an in silico framework. Molecular docking analysis revealed that isotrilobine possessed the highest binding affinity toward EGFR, achieving a docking score of -10.5 kcal/mol, indicating potent interactions within the active site. Molecular dynamics simulations over a 100 ns trajectory demonstrated that the EGFR-isotrilobine complex maintained structural stability throughout, as evidenced by RMSD values of 0.193-1.223 Å, RMSF of 1.5 ± 1.1 Å, radius of gyration (Rg) of 4.597-4.918 Å, and a solvent-accessible surface area (SASA) of 772.3 Å². Hydrogen bond analysis identified an average of four stable interactions, reinforcing persistent ligand binding within the receptor pocket. Furthermore, MM-PBSA calculations yielded a binding free energy of 101.063 ± 127.26 kJ/mol, indicating energetically favorable binding. These findings suggest that isotrilobine and related BBIQ analogues exhibit significant potential as EGFR inhibitors for TNBC therapy, serving as viable candidates for further experimental validation and drug development.

References

1

[1] Bou Zerdan, M., et al. (2022). Triple Negative Breast Cancer: Updates on Classification and Treatment in 2021. Cancers, 14(5), 1253.

2

[2] Chakraborty, A., Taj, Z., Raashika, K., Singh, L. C., dan Chattopadhyay, I. (2026). In silico disruption of TGF-β signalling in AR-deficient triple-negative breast cancer via AMP-based therapeutics. In Silico Research in Biomedicine, 2, 100163.

3

[3] Ndacyayisenga, J., Tolo, F. M., Wamunyokoli, F., dan Maina, E. N. (2024). Effects of tea catechin extracts on gene expression in TNBC: In silico and in vitro study. Informatics in Medicine Unlocked, 46, 101469.

4

[4] Vyshnavi, H., dan Namboori, K. (2023). Identifying potential ligand molecules targeting EGFR in TNBC. Research in Pharmaceutical Sciences, 18(2), 121–137.

5

[5] Garcia, A. R., et al. (2023). Abrogating metastatic properties of TNBC cells by EGFR and PI3K dual inhibitors. Cancers, 15(15), 3973.

6

[6] Rosado-Galindo, H., dan Domenech, M. (2023). Surface roughness modulates EGFR signaling and stemness of TNBC cells. Frontiers in Cell and Developmental Biology, 11, 1124250.

7

[7] Atanasov, A. G., et al. (2015). Discovery and resupply of pharmacologically active plant-derived natural products: A review. Biotechnology Advances, 33, 1582–1614.

8

[8] Newman, D. J. (2022). Natural products and drug discovery. National Science Review, 9(11), nwac206.

9

[9] Naeem, A., Hu, P., Yang, M., Zhang, J., Liu, Y., Zhu, W., & Zheng, Q. (2022). Natural products as anticancer agents: Current status and future perspectives. Molecules, 27(23), 8367.

10

[10] Jiang, Y., Liu, M., Liu, H., dan Liu, S. (2020). Traditional uses, phytochemistry, pharmacology and toxicology of Stephania tetrandra. Plant Cell, Tissue and Organ Culture, 141, 1–19.

11

[11] Jiang, F., Ren, S., Chen, Y., Zhang, A., Zhu, Y., Zhang, Z., Piao, D. (2021). Fangchinoline exerts antitumour activity by suppressing EGFR-PI3K/AKT pathway. Oncology Reports, 45(1), 139–150.

12

[12] Zhang, W., Yang, S., Liu, J., Bao, L., Lu, H., Li, H., Pan, W., Jiao, Y., He, Z. and Liu, J (2019). Screening antiproliferative drug from BBIQ alkaloids. BMC Cancer, 19, 6146.

13

[13] Yang, Y., et al. (2022). Network pharmacology and molecular docking-based mechanism study. Frontiers in Pharmacology, 12, 799448.

14

[14] Mortuza, M. G., et al. (2023). Computational study on alkaloids as inhibitors. Biochemistry Research International, 2023, 9975275.

15

[15] Gurung, A. B., Ali, M. A., Lee, J., Farah, M. A., dan Al-Anazi, K. M. (2021). Molecular docking and dynamics simulation study of bioactive compounds. PLOS One, 16(7), e0254035.

16

[16] Nerdy, N. N., P Lestari, P. L., F Fahdi, F. F., EDL Putra, E. D. L., SAB Amir, S. A. B., F Yusuf, F. Y., & TK Bakri, T. K. (2022). In silico studies of sesquiterpene lactones on EGFR and VEGFR. Pharmacognosy Journal, 14(1), 91–97.

17

[17] Magesh, K. T., dan Chandrasekharan, D. (2023). Novel therapeutic targets for oral cancer: In silico docking study. Journal of Orofacial Sciences, 15(2), 152–155.

18

[18] Elekofehinti, O.O., Adetoyi, I.R., Popoola, H.O., Ayodeji, F.O., Taiwo, F.A., Akinjiyan, M.O., Koledoye, O.F., Iwaloye, O. and Adegboyega, A.E. (2024). Discovery of potential EGFR inhibitors from black pepper. In Silico Pharmacology, 12(1), 197.

19

[19] Monmai, C., Sabuakham, S., Pabuprapap, W., Chaichompoo, W., Suksamrarn, A., Mahalapbutr, P (2025). Asiatic acid as a potent EGFR inhibitor. Biomolecules, 15(10), 1410.

20

[20] Mosharaf, M. P., Reza, M. S., Kibria, M. K., Ahmed, F. F., Kabir, M. H., Hasan, S., & Mollah, M. N. H. (2022). Computational identification of host genomic biomarkers highlighting their functions, pathways and regulators that influence SARS-CoV-2 infections and drug repurposing. Scientific reports, 12(1), 4279.

21

[21] Paez, S. V., Durango, D., dan Quiñones, W. (2024). In vivo and in silico evaluation study. RSC Advances, 14(53), 39325–39336.

22

[22] Millan-Casarrubias, E. J., García-Tejeda, Y. V., González-De la Rosa, C. H., Ruiz-Mazón, L., Hernández-Rodríguez, Y. M., & Cigarroa-Mayorga, O. E. (2025). Molecular docking evaluation of HER2-targeted therapies. Current Issues in Molecular Biology, 47(3).

23

[23] Lakhnotra, D. K., Maheta, J. B., Bhola, Y. O., Socha, B. N., Shaikh, N. H., Dave, P. A., & Koradiya, S. B. (2026). Synthesis, spectroscopic characterization, and DFT-assisted molecular docking analysis of novel 1, 3, 4-oxadiazole–1, 2, 3-triazole hybrids with antimicrobial and cytotoxicity potential. RSC advances, 16(7), 6314-6337.

24

[24] Ding, B., Wang, X., Zhang, Z., Wang, Y., Bo, W., Zhang, M., Zhang, M. (2025). Interactions between lncRNAs and MAPK signaling pathways. BMC Cancer, 25.

25

[25] Gupta, P., Mohammad, T., Dahiya, R., Roy, S., Noman, O. M. A., Alajmi, M. F., Hassan, M. I. (2019). Evaluation of binding mechanism of phytochemicals. Scientific Reports, 9.

26

[26] Dahiya, R., Mohammad, T., Gupta, P., Haque, A., Alajmi, M. F., Hussain, A., & Hassan, M. I. (2019). Molecular interaction studies on anticancer compounds. RSC Advances, 9.

27

[27] Ghahremanian, S., et al. (2022). Molecular dynamics simulation approach for drug discovery. Journal of Molecular Liquids, 360.

28

[28] Saravanan, V., Chagaleti, B. K., Packiapalavesam, S. D., Kathiravan, M. (2024). Ligand based pharmacophore modelling and integrated computational approaches in the quest for small molecule inhibitors against hCA IX. RSC advances, 14(5), 3346-3358.

29

[29] Gopinath, P., dan Kathiravan, M. K. (2021). Docking and MD simulation of sulfonamide derivatives. RSC Advances, 11, 38079–38093.

30

[30] Azmal, M., Paul, J. K., Prima, F. S., Talukder, O. F., & Ghosh, A. (2024). In silico molecular docking study targeting RAS pathway. PLOS One, 19(9).

31

[31] Li, D. D., Wu, T. T., Yu, P., Wang, Z. Z., Xiao, W., Jiang, Y., & Zhao, L. G. (2020). Molecular dynamics analysis of EGFR inhibitors. ACS Omega, 5(26), 16307–16314.

32

[32] Venugopal, S., dan K., D. (2024). Molecular docking and simulation of terpenes. Frontiers in Bioinformatics, 4.

33

[33] Elfiky, A. A., Mahran, H. A., Ibrahim, I. M., Ibrahim, M. N., & Elshemey, W. M. (2022). Molecular dynamics simulations and MM-GBSA study. RSC Advances, 12(5), 2741–2750.

34

[34] Baruah, I., Kashyap, C., Guha, A. K., dan Borgohain, G. (2022). Interaction between polyphenols and β-lactoglobulin. ACS Omega, 7(27), 23083–23095.

35

[35] Salamat, A., Kosar, N., Mohyuddin, A., Imran, M., Zahid, M. N., Mahmood, T. (2024). Molecular docking and MD simulation of natural inhibitors. Molecules, 29(5).

36

[36] Alsaady, I. M., Gattan, H. S., Aljahdali, S. M., Alruhaili, M. H., Dwivedi, V. D., Azhar, E. I. (2026). Conformational dynamics and binding free energy analyses unveil a stable flavonoid inhibitor of dengue virus NS5 polymerase. Scientific Reports.

37

[37] Kolybalov, D. S., Kadtsyn, E. D., & Arkhipov, S. G. (2024). Structure-based drug design of inhibitors. Computation, 12(1).

38

[38] Zikri, A. T., Pranowo, H. D., dan Haryadi, W. (2021). Stability and hydrogen bond occupancy analysis. Indonesian Journal of Chemistry, 21(2), 383–390.

39

[39] Halimi, M., dan Bararpour, P. (2022). Natural inhibitors study using MD simulation. Journal of Molecular Modeling, 28(9).

40

[40] Park, J. H., Liu, Y., Lemmon, M. A., dan Radhakrishnan, R. (2012). Erlotinib binds EGFR kinase domain. Biochemical Journal, 448(3), 417–423

In Silico Evaluation of Bisbenzylisoquinoline Compounds from Stephania sp. as EGFR Inhibitors for Triple-Negative Breast Cancer

Abstract

References

How to Cite

Most read articles by the same author(s)

In Silico Evaluation of Bisbenzylisoquinoline Compounds from Stephania sp. as EGFR Inhibitors for Triple-Negative Breast Cancer

Abstract

References

How to Cite

Cite Article

Article Update

Most read articles by the same author(s)