Enade Perdana Istyastono(1*), Nunung Yuniarti(2)

(1) Division of Drug Design and Discovery, Faculty of Pharmacy, Sanata Dharma University
(2) Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Gadjah Mada
(*) Corresponding Author


Phytoestrogens have some important biological effects and could be employed as medicinal resources, for example as cancer chemopreventive agents. Phytoestrogen is defined as a phytochemical that has estrogenic or anti estrogenic effects. However, there is no database providing comprehensive list of phytoestrogen structures. In computer-aided drug discovery, the database is required to perform virtual screening for retrospective validation and structure-based drug design. The research presented in this article attempted to collect a comprehensive list of phytoestrogen structures. Subsequently, the structures were prepared in their three dimensional structures using SPORES1.3 for molecular docking simulations using PLANTS1.2. The ready-to-dock structures were then stored online as and could be downloaded from This database contains 30 ready-to-dock unique phytoestrogens with total of 53 different configurations.


Phytoestrogen, database, drug discovery, molecular docking

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Ali, S. and Coombes, R.C. 2000. Estrogen receptor alpha in human breast cancer: occurrence and significance. J. Mammary Gland Biol. Neoplasia 5: 271–281.

Anita, Y., Radifar, M., Kardono, L., Hanafi, M. and Istyastono, E.P. 2012. Structure-based design of eugenol analogs as potential estrogen receptor antagonists. Bioinformation 8: 901–906.

Anita, Y., Sundowo, A., Dewi, N.L.P., Filailla, E., Mulyani, H., Risdian, C., Banjarnahor, S., Hanafi, M. and Istyastono, E.P. 2015. Biotransformation of eugenol to dehydroeugenol catalyzed by Brassica juncea peroxidase and its cytotoxicity activities. Procedia Chem. 16: 265–271.

Balunas, M.J., Su, B., Brueggemeier, R.W. and Kinghorn, A.D. 2008. Xanthones from the botanical dietary supplement mangosteen (Garcinia mangostana) with aromatase inhibitory activity. J. Nat. Prod. 71: 1161–1166.

Bento, A.P., Gaulton, A., Hersey, A., Bellis, L.J., Chambers, J., Davies, M., Krüger, F.A., Light, Y., Mak, L., McGlinchey, S., Nowotka, M., Papadatos, G., Santos, R. and Overington, J.P. 2014. The ChEMBL bioactivity database: An update. Nucl. Acids Res. 42: 1083–1090.

Brusotti, G., Cesari, I., Dentamaro, A., Caccialanza, G. and Massolini, G. 2014. Isolation and characterization of bioactive compounds from plant resources: The role of analysis in the ethnopharmacological approach. J. Pharm. Biomed. Anal. 87: 218–228.

Cardoso, F. and Senkus, E., 2015. Breast cancer in 2014: A call back to reality! Nat. Rev. Clin. Oncol. 12, 67–68.

Dixon, R.A. 2004. Phytoestrogens. Annu. Rev. Plant Biol. 55: 225–261.

Efferth, T. and Koch, E. 2011. Complex interactions between phytochemicals. The multi-target therapeutic concept of phytotherapy. Curr. Drug Targets 12: 122–132.

Helferich, W.G., Andrade, J.E. and Hoagland, M.S. 2008. Phytoestrogens and breast cancer: a complex story. Inflammopharmacology 16: 219–26.

Irwin, J.J., Sterling, T., Mysinger, M.M., Bolstad, E.S. and Coleman, R.G., 2012. ZINC: A free tool to discover chemistry for biology. J. Chem. Inf. Model. 52: 1757–1768.

Istyastono, E.P. 2015. Employing recursive partition and regression tree method to increase the quality of structure-based virtual screening in the estrogen receptor alpha ligands identification. Asian J. Pharm. Clin. Res. 8: 21–24.

Istyastono, E.P., Kooistra, A.J., Vischer, H., Kuijer, M., Roumen, L., Nijmeijer, S., Smits, R., de Esch, I., Leurs, R. and de Graaf, C., 2015a. Structure-based virtual screening for fragment-like ligands of the G protein-coupled histamine H4 receptor. Med. Chem. Commun. 6: 1003–1017.

Istyastono, E.P., Riswanto, F.D.O., and Yuliani, S.H. 2015b. Computer-aided drug repurposing: a cyclooxygenase-2 inhibitor celecoxib as a ligand for estrogen receptor alpha. Indones. J. Chem. 15: 274–280.

Istyastono, E.P. and Setyaningsih, D., 2015. Construction and retrospective validation of structure-based virtual screening protocols to identify potent ligands for human adrenergic β2 receptor. Indones. J. Pharm. 26: 20–28.

Korb, O., Stützle, T. and Exner, T.E., 2007. An ant colony optimization approach to flexible protein–ligand docking. Proc. IEEE Swarm Intell. Symp. 1: 115–134.

Korb, O., Stützle, T. and Exner, T.E., 2009. Empirical scoring functions for advanced protein-ligand docking with PLANTS. J. Chem. Inf. Model. 49: 84–96.

Kufareva, I., Katritch, V., Stevens, R.C. and Abagyan, R. 2014. Advances in GPCR modeling evaluated by the GPCR DOCK 2013 assessment: Meeting new challenges. Structure 22: 1120–1139.

Lill, M.A. and Danielson, M.L. 2011. Computer-aided drug design platform using PyMOL. J. Comput. Aided Mol. Des. 25: 13–19.

Matsuda, H., Shimoda, H., Morikawa, T. and Yoshikawa, M. 2001. Phytoestrogens from the roots of Polygonum cuspidatum (Polygonaceae): Structure-requirement of hydroxyanthraquinones for estrogenic activity. Bioorg. Med. Chem. Lett. 11: 1839–1842.

Mysinger, M.M., Carchia, M., Irwin, J.J. and Shoichet, B.K. 2012. Directory of Useful Decoys, Enhanced (DUD-E): Better ligands and decoys for better benchmarking. J. Med. Chem. 55: 6582–6594.

O’Boyle, N.M., Banck, M., James, C.A., Morley, C., Vandermeersch, T., and Hutchison, G.R. 2011. Open Babel: An open chemical toolbox. J. Cheminform. 3: 33–47.

Pathania, S., Ramakrishnan, S.M. and Bagler, G. 2015. Phytochemica: A platform to explore phytochemicals of medicinal plants. Database 10.1093/database/bav075: 1–8.

Radifar, M., Yuniarti, N., Istyastono, E.P. 2013. PyPLIF: Python-based protein-ligand interaction fingerprinting. Bioinformation 9: 325–328.

Setiawati, A., Riswanto, F.D.O., Yuliani, S.H. and Istyastono, E.P. 2014a. Retrospective validation of a structure-based virtual screening protocol to identify ligands for estrogen receptor alpha and its application to identify the alpha-mangostin binding pose. Indo. J. Chem. 14: 103–108.

Setiawati, A., Riswanto, F.O.D., Yuliani, S.H. and Istyastono, E.P. 2014b. Anticancer activity of mangosteen pericarp dry extract against MCF-7 breast cancer cell line though estrogen receptor-α. Indones. J. Pharm. 25: 119–124.

Shiau, A.K., Barstad, D., Loria, P.M., Cheng, L., Kushner, P.J., Agard, D.A. and Greene, G.L. 1998. The structural basis of estrogen receptor/coactivator recognition and the antagonism of this interaction by tamoxifen. Cell 95: 927–937.

Shibata, M.-A., Iinuma, M., Morimoto, J., Kurose, H., Akamatsu, K., Okuno, Y., Akao, Y. and Otsuki, Y. 2011. α-Mangostin extracted from the pericarp of the mangosteen (Garcinia mangostana Linn) reduces tumor growth and lymph node metastasis in an immunocompetent xenograft model of metastatic mammary cancer carrying a p53 mutation. BMC Med. 9: 69.

ten Brink, T. and Exner, T.E., 2009. Influence of protonation, tautomeric, and stereoisomeric states on protein-ligand docking results. J. Chem. Inf. Model. 49: 1535–1546.

Varinska, L., Gal, P., Mojzisova, G., Mirossay, L. and Mojzis, J. 2015. Soy and breast cancer: Focus on angiogenesis. Int. J. Mol. Sci. 16: 11728–11749.

Vidhya, N. and Devaraj, S.N. 2011. Induction of apoptosis by eugenol in human breast cancer cells. Indian J. Exp. Biol. 49: 871–878.


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