Insight on Estrogen Receptor Alpha Modulator from Indonesian Herbal Database: An in-silico analysis
DOI:
https://doi.org/10.30595/pharmacy.v17i2.7592Keywords:
Estrogen receptor α, Indonesian herbal database, molecular docking, pharmacophoreAbstract
Estrogen receptor α (ERα) is liable for regulating transcription factors which are an important part of hormonal signaling in breast cancer. This study intends to find hit compounds that are considered capable of inhibiting ERα by utilizing structure-based pharmacophores and molecular docking. Pharmacophore of the original ERα ligand (E4D600) has one hydrogen bond acceptor and three hydrogen bond donors which are used to select compounds from the Indonesian herbal database. This pharmacophore model had an Area under Curve of the Receiver Operating Characteristics (AUC-ROC) value is 0.80 and the Goodness of Hits (GH) value is 0.81. The selection process generated 330 compounds which proceed to the molecular docking stage to analyze their binding energy and interactions to ERα. The results indicated potential hit compounds seen from their binding energies in the range -5.42 to -10.01 kcal/mol. four of the best compounds including Lig57/(-)-Bidwillon A, Lig47/Quercetin 3-(6''-galloylgalactoside), Lig197/Multifloroside and Lig83/Erythrabyssin II provide promising information for their detailed analysis as ERα inhibitors.
References
Arba, M., Yamin, S. Ihsan, and D.H. Tjahjono. 2018. “Computational Approach toward Targeting the Interaction of Porphyrin Derivatives with Bcl-2.” Journal of Applied Pharmaceutical Science 8 (12). https://doi.org/10.7324/JAPS.2018.81208.
Arba, Muhammad, Andry Nur-Hidayat, Slamet Ibrahim Surantaadmaja, and Daryono H. Tjahjono. 2018. “Pharmacophore-Based Virtual Screening for Identifying Β5 Subunit Inhibitor of 20S Proteasome.” Computational Biology and Chemistry 77: 64–71. https://doi.org/10.1016/j.compbiolchem.2018.08.009.
Batool, Maria, Bilal Ahmad, and Sangdun Choi. 2019. “A Structure-Based Drug Discovery Paradigm.” International Journal of Molecular Sciences 20 (11). https://doi.org/10.3390/ijms20112783.
Dai, Xue, and Jie Wu. 2011. “Selective Estrogen Receptor Modulator: Raloxifene.” Journal of Reproduction and Contraception 22 (1): 51–60. https://doi.org/10.1016/S1001-7844(12)60007-8.
Grande, Fedora, Bruno Rizzuti, Maria A. Occhiuzzi, Giuseppina Ioele, Teresa Casacchia, Fabrizio Gelmini, Rita Guzzi, Antonio Garofalo, and Giancarlo Statti. 2018. “Identification by Molecular Docking of Homoisoflavones from Leopoldia Comosa as Ligands of Estrogen Receptors.” Molecules 23 (4): 1–14. https://doi.org/10.3390/molecules23040894.
Haque, Md Moquitul, and Kartiki V. Desai. 2019. “Pathways to Endocrine Therapy Resistance in Breast Cancer.” Frontiers in Endocrinology 10 (August): 1–7. https://doi.org/10.3389/fendo.2019.00573.
Hua, Hui, Hongying Zhang, Qingbin Kong, and Yangfu Jiang. 2018. “Mechanisms for Estrogen Receptor Expression in Human Cancer 11 Medical and Health Sciences 1112 Oncology and Carcinogenesis 06 Biological Sciences 0604 Genetics.” Experimental Hematology and Oncology 7 (1): 1–11. https://doi.org/10.1186/s40164-018-0116-7.
Jia, Min, Karin Dahlman-Wright, and Jan Åke Gustafsson. 2015. “Estrogen Receptor Alpha and Beta in Health and Disease.” Best Practice and Research: Clinical Endocrinology and Metabolism 29 (4): 557–68. https://doi.org/10.1016/j.beem.2015.04.008.
Kim, Seongkon, Jane Y. Wu, Elizabeth T. Birzin, Katalin Frisch, Wanda Chan, Lee Yuh Pai, Yi Tien Yang, et al. 2004. “Estrogen Receptor Ligands. II. Discovery of Benzoxathiins as Potent, Selective Estrogen Receptor α Modulators.” Journal of Medicinal Chemistry 47 (9): 2171–75. https://doi.org/10.1021/jm034243o.
Kucinska, Malgorzata, Maria Dolores Giron, Hanna Piotrowska, Natalia Lisiak, Walter H. Granig, Francisco Javier Lopez-Jaramillo, Rafael Salto, Marek Murias, and Thomas Erker. 2016. “Novel Promising Estrogenic Receptor Modulators: Cytotoxic and Estrogenic Activity of Benzanilides and Dithiobenzanilides.” PLoS ONE 11 (1): 1–16. https://doi.org/10.1371/journal.pone.0145615.
Li, H, K Leung, and M Wong. 2012. “Idock: A Multithreaded Virtual Screening Tool for Flexible Ligand Docking.” In 2012 IEEE Symposium on Computational Intelligence in Bioinformatics and Computational Biology (CIBCB), 77–84. https://doi.org/10.1109/CIBCB.2012.6217214.
Makrynitsa, Garyfallia I, Michail Lykouras, Georgios A Spyroulias, and Minos-Timotheos Matsoukas. 2018. “In Silico Drug Design” ELS, no. August: 1–7. https://doi.org/10.1002/9780470015902.a0028112.
Morris, Garrett M, Ruth Huey, William Lindstrom, Michel F Sanner, Richard K Belew, David S Goodsell, and Arthur J Olson. 2009. “AutoDock4 and AutoDockTools4: Automated Docking with Selective Receptor Flexibility.” Journal of Computational Chemistry 30 (16): 2785–91. https://doi.org/10.1002/jcc.21256.
Mysinger, Michael M, Michael Carchia, John. J Irwin, and Brian K Shoichet. 2012. “Directory of Useful Decoys, Enhanced (DUD-E): Better Ligands and Decoys for Better Benchmarking.” Journal of Medicinal Chemistry 55 (14): 6582–94. https://doi.org/10.1021/jm300687e.
Piperigkou, Zoi, and Nikos K. Karamanos. 2020. “Estrogen Receptor-Mediated Targeting of the Extracellular Matrix Network in Cancer.” Seminars in Cancer Biology 62 (July): 116–24. https://doi.org/10.1016/j.semcancer.2019.07.006.
Sholikhah, Eti Nurwening. 2016. “Indonesian Medicinal Plants as Sources of Secondary Metabolites for Pharmaceutical Industry.” Journal of Thee Medical Sciences (Berkala Ilmu Kedokteran) 48 (04): 226–39. https://doi.org/10.19106/jmedsci004804201606.
Souza, Paulo C.T., Larissa C. Textor, Denise C. Melo, Alessandro S. Nascimento, Munir S. Skaf, and Igor Polikarpov. 2017. “An Alternative Conformation of ERβ Bound to Estradiol Reveals H12 in a Stable Antagonist Position.” Scientific Reports 7 (1): 1–11. https://doi.org/10.1038/s41598-017-03774-x.
Tjindarbumi, Didid, and Rukmini Mangunkusumo. 2002. “Cancer in Indonesia, Present and Future.” Japanese Journal of Clinical Oncology 32 (Supplement 1): S17-21. https://doi.org/10.1093/jjco/hye123.
Wolber, Gerhard, and Thierry Langer. 2005. “LigandScout: 3-D Pharmacophores Derived from Protein-Bound Ligands and Their Use as Virtual Screening Filters.” Journal of Chemical Information and Modeling. https://doi.org/10.1021/ci049885e.
Zheng, Ze Yi, Meenakshi Anurag, Jonathan T. Lei, Jin Cao, Purba Singh, Jianheng Peng, Hilda Kennedy, et al. 2020. “Neurofibromin Is an Estrogen Receptor-α Transcriptional Co-Repressor in Breast Cancer.” Cancer Cell 37 (3): 387-402.e7. https://doi.org/10.1016/j.ccell.2020.02.003.
Downloads
Published
How to Cite
Issue
Section
License
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution 4.0 International License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).
