In Silico Prediction of Heliannuol A, B, C, D, and E Compounds on Estrogen Receptor β Agonists

Roihatul Mutiah, Alif Firman Firdausy, Yen Yen Ari Indrawijaya, Hibbatullah Hibbbatullah


Heliannuols has a benzoxepine ring that produces anticancer activity by the inhibition mechanism of phosphoinositide 3 kinases (PI3K). Heliannuols are a compound that can be found in the leaves of sunflower (Helianthus annuus L.). The purpose of this study is to predict interactions, toxicity, physicochemical, and pharmacokinetics of Heliannuol A, B, C, D, and E based in silico as candidate anticancer drugs. Estrogen receptor beta (ERβ) is a new potential therapy for glioma with an antiproliferative effect. Ligands agonist ERβ have the potential activity to inhibit the proliferation of glioma cells and the discovery of this ligand has opened new therapy through the ERβ to prolong survival in cancer patients. Prediction of physicochemical properties based on Lipinski rules and penetrate in the blood-brain barrier. Receptor validation shows that 2I0G(A) has a smaller RMSD value than 2I0G(B), receptor validation is valid if the RMSD value less than 2. The result of molecular docking shows that Heliannuols comply with Lipinski rules and have low toxicity. Heliannuols also have a similar amino acid with Erteberel, but the rerank score of Erteberel still lower than Heliannuols.

Keywords: Helianthus annuus, Heliannuols, estrogen receptor β (ERβ), in silico, toxicity.

Full Text:



Ceccarini, 2004, Essential Oil Composition of Helianthus Annus L. Leaves and Heads of Two Cultivated Hybrids ‘Carlos and Florom 350, Industrial Crops and Products.

Chakraborty, P. and Ramakrishnan, M., 2016, Role of P-Glycoprotein in Chemotherapeutic Drug Resistance and Mechanisms of Pump Deactivation to Overcome MDR in Cancer Cells A Critical Review, Frontiers in Biomedical Science, 1(2), 8.

Chander, S., Tang, C.R., Al-Maqtari, H.M., Jamalis, J., Penta, A., Hadda, T.B., Sirat, H.M., Zheng, Y.T. and Sankaranarayanan, M., 2017, Synthesis and Study of Anti-HIV-1 RT Activity of 5-Benzoyl-4Methyl-1,3, 4,5-Tetrahydro-2h-1,5-Benzodia-zepin-3-One Derivates, Bioorg Chem, 72, 74–79. CrossRef

El-Din, H.M.A., Loutfy, S.A., Fathy, N., Elberry, M.H., Mayla, M.A., Kassem, S. and Naqvi, A., 2016, Molecular Docking Based Screening of Compounds Against VP40 Ebola Virus, Bioinformation, 12(3), 192-196. CrossRef

Ghantous, A., Gali-Muhtasib, H., Vuorela, H., Saliba, N.A. and Darwiche, N., 2010, What Made Sesquiterpene Lactones Reach Cancer Clinical Trials?, Drug Discovery Today, 15(15–16), 668–678. CrossRef

Hardjono, S., 2012, Modiikasi Struktur 1-(Benzoiloksi)Urea dan Hubungan Kuantitatif Struktur Aktivitas Sitotoksiknya, Surabaya: Universitas Airlangga. Link

Hardjono, S., Siswandono, and Andayani, R., 2017, Evaluation of N-Benzoylthiourea Derivatives as Possible Analgesic Agents by Predicting Their Hysicochemical and Pharmacokinetic Properties, Toxicity, and Analgesic Activity, Indonesian Journal of Biotechnology, 22(2), 76-85. CrossRef

Hartman J., Edvardsson, K., Lindberg K., Zhao, C., Williams, C., Strom, A. and Gustafsson, J-A., 2009, Tumor Repressive Functions of Estrogen Receptor Beta in SW480 Colon Cancer Cells, Cancer Res, 69(15), 6100-6106. CrossRef

Heffron, T.P., Wei, B., Olivero, A., Staben, S.T., Tsui, V. and Do, S., 2011, Rational Design of Phosphoinositide 3-Kinase A Inhibitors That Exhibit Selectivity Over the Phosphoinositide 3-Kinase B Isoform, J. Med. Chem, 54(22), 7815–7833. CrossRef

Hughes, R.G., 2008, Patient Safety and Quality: An Evidence Base Handbook for Nurses, Rochville MD: Agency for Healthcare Research and Quality Publication. CrossRef

Kelder, J., Grootenhuis, P.D., Bayada, D.M., Delbressine, L.P. and Ploemen, J.P., 1999, Polar Molecular Surface as A Dominating Determinant for Oral Absorption and Brain Penetration of Drugs, Pharmaceutical Research, 16(10), 1514-1519. CrossRef

Koepsell, H., 2015, Role of Organic Cation Transporters in Drug-Drug Interaction, Expert Opin Drug Metab Toxicol, 11(10), 1619-1633. CrossRef

Kuntala, N., Telu, J.R., Anireddy, J.S. and Pal, S., 2017, A Brief Overview on Chemistry and Biology of Benzoxepine, Letters in Drug Design and Discovery, 14(9), 1–13. CrossRef

Lipinski, C.A., Lombardo, F., Dominy, B.W. and Feeney, P.J., 2001, Experimental and Computational Approaches to Estimate Solubility and Permeability in Drug Discovery and Development Settings, Advanced Drug Delivery Reviews, 46(1-3), 3–26. CrossRef

Macias, F.A., Molinillo, J.M.G., Varela, R.M. and Torres, A., 1994, Structural Eludation and Chemistry of A Novel Family of Bioactive Sesquiterpenes: Heliannuols, J. Org. Chem, 59, 8261–66. CrossRef

Macias, F.A., Varela, R.M., Torres, A. and Molinillo, J.M.G., 2000, Potential Allelopathic Activity of Natural Plant Heliannes: A Proposal of Absolute Configuration and Nomenclature, Journal of Chemical Ecology, 26(9), 2173-2186.

Macias, F.A., Torres, A., Galindo, J.L.G., Varela, R.M., Alvarez, J.A. and Molinillo, J.M.G., 2002, Bioactive Terpenoids from Sunflower Leaves Cv. Peredovick, Phytochemistry, 61(6), 687–692. CrossRef

Meegan, M.J. and Lloyd, D.G., 2003, Advances in The Science of Estrogen Receptor Modulation, Curr Med Chem, 10(3), 181-210. CrossRef

Muchtaridi, Yanuar, A., Megantara, S. and Purnomo, H., 2018, Kimia Medisinal: Dasar Dasar Dalam Perancangan Obat Edisi Pertama, Jakarta: Prenada Media Group. Link

Nilsson S. and Gustafsson J.A., 2011, Estrogen Receptors: Therapies Targeted to Receptor Subtypes, Clin Pharmacol Ther, 89(1), 44-55. CrossRef

Ren, W., Qiao Z., Wang H., Zhu L., and Zhang L., 2003, Flavonoids, Promising Anticancer Agents, Med Res Rev., 23(4), 519-534. CrossRef

Robert, J. and Jarry, C., 2003, Multidrug Resistance Reversal Agents, Journal Med Chem., 46(23), 4805–4817. CrossRef

Ruswanto, 2015, Molecular Docking Empat Turunan Isonicotinohydrazide Pada Mycobacterium Tuberculosis Enoyl-Acyl Carrier Protein Reductase (InhA), Jurnal Kesehatan Bakti Tunas Husada: Jurnal Ilmu-ilmu Keperawatan, Analis Kesehatan dan Farmasi, 13(1), 135-141. CrossRef

Saini, S., and Sharma, S., 2011, Helianthus Annuus (Asteraceae): A Review, International Journal of Pharma Professional’s Research, 2(4), 381-386. CrossRef

Sareddy, G.R., Nair, B.C., Gonugunta, V.K., Zhang, Q-g., Brenner, A., Brann, D.W., Tekmal, R.R. and Vadlamudi, R.K., 2012, Therapeutic Significance of Estrogen Receptor β Agonists in Gliomas, Molecular Cancer Therapeutics, 11(5), 1174–82. CrossRef

Sareddy, G.R. and Vadlamudi, R.K., 2015, Cancer Therapy Using Natural Ligands That Target Estrogen Receptor Beta, Chinese Journal of Natural Medicines, 13(11), 801–7. CrossRef

Sareddy, G.R., Li, X., Liu, J., Viswanadhapalli, S., Garcia, L., Gruslova, A., Cavazos, D., et al., 2016, Selective Estrogen Receptor β Agonist LY500307 as a Novel Therapeutic Agent for Gliolastoma, Scientific Report, 6, 24185. CrossRef

Siswandono, 2011, Studi Pemodelan Molekul Interaksi Beberapa Turunan Penisilin Dengan Reseptor DD-Transpeptidase Dari Streptomyces R61(1PWC), Airlangga Journal of Pharmacy, 9(2), 33–41. Link

Strom, A., Hartman, J., Foster, J.S., Kietz, S., Wimalasena, J. and Gustafsson, J-A., 2004, Estrogen Receptor Beta Inhibits 17Beta-Estradiol-Stimulated Proliferation of the Breast Cancer Cell Line T47D, Proc Natl Acad Sci USA, 101(6), 1566-1571. CrossRef

Wijaya, K., Tahir, I. and Harnowo, 2003, Studi Mekanisme Migrasi Proton Ganda Pada Struktur Supermolekul Asam Asetat-Air Dan Asam Asetat-Ammoniak Dengan Metode Ab Initio, Indonesian Journal of Chemistry, 3(2), 102-110.


Copyright (c) 2021 Hibbatullah Hibbbatullah

Indexed by:




Indonesian Society for Cancer Chemoprevention