In Silico Study on the Effect of Heliannuol A, B, C, D, E Compounds of Sunflower (Helianthus annuus L.) on Dual PI3K/mTOR (5OQ4) Enzyme

Roihatul Mutiah(1*), Yen Yen Ari Indrawijaya(2), Tanaya Jati Dharma(3), Jamilah Damaiyanti(4)

(1) Pharmacy Study Program, Faculty of Medicine and Health Sciences, Maulana Malik Ibrahim State Islamic University of Malang
(2) Pharmacy Study Program, Faculty of Medicine and Health Sciences, Maulana Malik Ibrahim State Islamic University of Malang
(3) Pharmacy Study Program, Faculty of Medicine and Health Sciences, Maulana Malik Ibrahim State Islamic University of Malang
(4) Pharmacy Study Program, Faculty of Medicine and Health Sciences, Maulana Malik Ibrahim State Islamic University of Malang
(*) Corresponding Author


Heliannuol is a sesquiterpene that has a benzoxepine ring, oxepin. Many derivatives of benzoxepine compounds show anticancer activity by inhibiting the phosphoinositide 3-kinase (PI3K) enzyme. These enzymes play a role in cell proliferation and growth. The study aims to predict the physicochemical properties using Lipinski’s Rule of Five parameters on phosphoinositide 3- kinase (PI3K/Mtor; PDB 5OQ4) enzyme and the toxicity of Heliannuol A, B, C, D, E compounds. The process uses the pkCSM online toolThe validation of receptor 5OQ4 is done using the value parameter RMSD < 2 (Å). Protox online tool dan pkCSM online tool is employed to predict the toxicity using parameter LD50, skin sensitization, Ames toxicity, hepatotoxicity, and toxicity class. The interaction of ligan and enzyme is tested using Molegro Virtual Docker 6.0. Heliannoul A, B, C, D, E compounds fulfill Lipinski’s Rule of Five. The receptor 5OQ4 is known valid using the value of RMSD 0,923 (Å). Heliannuol A, B, C, D, E compounds inhibit Dual PI3K / mTOR enzyme less than Bimiralisib. As a result of the toxicity test of compounds Helliannouls A, B, C, E, and Bimiralisib compounds are included in class 4, while Helliannouls D compounds are included in class 5.


in-silico; Heliannuols; PI3K/mTOR; glioblastoma

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An, Zhenyi, Ozlem Aksoy, Tina Zheng, Qi-Wen Fan, William A. Weiss., 2018, ‘Epidermal Growth Factor Receptor And Egfrviii In Glioblastoma: Signaling Pathways And Targeted Therapies’, Oncogene 37:1561–1575

Bianchi L, E. De Micheli, A. Bricolo, C. Ballini, M. Fattori, C. Venturi, F. Pedata, K. F. Tipton, and L. Della Corte., 2004, ‘Extracellular Levels of Amino Acids and Choline in Human High-Grade Gliomas: An Intraoperative Microdialysis Study,' Neurochemical Research. Vol. 29, No. 1

Dermawan,Doni; Riyadi Sumirtanurdin; Deti Dewantisari.2019. Molecular Dynamics Simulation of Estrogen Receptor Alpha Against Andrografolid as Anti Breast Cancer. Indonesian Journal of Pharmaceutical Science and Technology. 6(2),65-76

Hardjono, Suko., 2016, ‘Prediction of Pharmacokinetic Properties, Toxicity and Cytotoxic Activity of N Benzoyl-N’-(4-fluorophenyl) thiourea Derivatives as Anticancer Drugs Candidate through Molecular Modeling, Indonesian Journal of Pharmaceutical Sciences, 246-255 Vol. 14, No. 2

Heffron, T. P.; Wei, B.; Olivero, A.; Staben, S. T.; Tsui, V.; Do, S.; Dotson, J.; Folkes, A. J.; Goldsmith, P.; Goldsmith, R.; Gunzner, J.; Lesnick, J.; Lewis, C.; Mathieu, S.; Nonomiya, J.; Shuttleworth, S.; Sutherlin, D. P.; Wan, N. C.; Wang, S.; Wiesmann, C.; Zhu, B. Y., 2011, ‘Rational design of phosphoinositide 3-kinase α inhibitors that exhibit selectivity over the phosphoinositide 3-kinase’, J Med Chem. 54, 7815- 7833

Kuntala, Telu J, Anireddy dan Pal., 2017, ‘A Brief Overview on Chemistry and Biology of Benzoxepine,' Letters in Drug Design & Discovery. 14, 1-13

Ministry of Health Republic of Indonesia, 2017, 'National Guidelines for Brain Tumor Medicine Service'.

Lipinski, C.A., Lombardo, F., Dominy, B.W., dan Feeney, P.J., 2001, ‘Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings’, Advanced Drug Delivery Reviews. Volume 46: 3-26.

Muttaqin, Fauzan Zein; Halim Ismail; Hubbi Nasrullah Muhammad.,2019, ‘Study of Molecular   Docking,   Molecular    Dynamics, and derivative compounds Alkaloids Toxicity Prediction Naftiridin As Casein Protein Kinase Inhibitors 2-Α On Leukemia Cancer’,  Pharmacoscript, Volume 2 No. 1

Pelkonen, O., Turpeinen, M., dan Raunio, H., 2011, In Vivo In Vitro In Silico Pharmacokinetic Modelling in Drug Development, Clinical Pharmakokinetics. 50 (8): 483-491.

Siswandono.,2016, Medicinal Chemistry I Edition II, Surabaya: Airlangga University Press

Susanti, N. M. P., D. P. D. Saputra, P. L. Hendrayati, I. P. D. N. Parahyangan, I. A. D. G. Swandari.,2018, ‘Molecular Docking Cyanidine and Peonidine as Anti-Inflammatory    Atherosclerosis     in    SilicoJournal of Pharmacy Udayana. Vol 7 No.1

Zaidan, Sarah; Syamsudin; Deni Rahmat; Ratna Djamil., 2019, ‘Activity of Compounds in Sargassum sp. as Anti-atherosclerosis with Ligand-Receptor Comparison HMG-CoA Reductase Simvastatin (1HW9) and In-Silico Toxicity Test)’, Indonesian Journal of Pharmaceutical Sciences. Vol. 17, No. 1

Zhao, Hua-Fu; Jing Wang2; Wei Shao; Chang-Peng Wu; Zhong-Ping Chen2; Shing-Shun Tony To And Wei-Ping Li.,2017, ‘Recent Advances In The Use Of PI3K Inhibitors For Glioblastoma Multiforme: Current Preclinical And Clinical Development’, Molecular Cancer. 16:100


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