Molecular Docking Study of Akar Kuning (Arcangelisia flava) Secondary Metabolites as Src Inhibitor

Mohammad Rizki Fadhil Pratama, Evi Mulyani, Suratno Suratno


Proto-oncogene tyrosine-protein kinase Src is also known as simply Src is a tyrosine kinase protein which is one of the targets in various cancer therapies such as leukemia. Meanwhile, akar kuning (Arcangelisia flava) has gained significant attention as a medicinal plant that has a cytotoxic effect on various types of cancer cells. This study aims to determine the potential of secondary metabolites of akar kuning as Src inhibitors. Molecular docking was carried out using Autodock Vina 1.1.2 with 2HCK receptors, that quercetin and dasatinib were used as reference ligands. The docking results showed that the highest affinity was shown by berberine with a ΔG value of -9.0 kcal/mol, exceeded quercetin and dasatinib. However, the highest amino acid similarity to quercetin and dasatinib was produced by jatrorrhizine, with 93.33% and 73.91%, respectively. Interestingly, berberine is the ligand with the third-highest similarity after jatrorrhizine and palmatine, while jatrorrhizine has the second-highest affinity after berberine. The results concluded that the combination of berberine and jatrorrhizine is predicted to be optimally used as an Src inhibitor in cancer therapy.

Full Text:



Araujo, J. and Logothetis, C., 2010, Dasatinib: a potent SRC inhibitor in clinical development for the treatment of solid tumors, Cancer Treat. Rev., 36(6), 492-500. CrossRef

Ardito, F., Giuliani, M., Perrone, D., Troiano, G. and Muzio, L.L., 2017, The crucial role of protein phosphorylation in cell signaling and its use as targeted therapy (Review), Int. J. Mol. Med., 40(2), 271-280. CrossRef

Atkovska, K., Samsonov, S.A., Paszkowski-Rogacz, M. and Pisabarro, M.T., 2014, Multipose Binding in Molecular Docking, Int. J. Mol. Sci., 15(2), 2622-2645. CrossRef

Bhullar, K.S., Lagaron, N.O., McGowan, E.M., Parmar, I., Jha, A., Hubbard, B.P. and Rupasinghe, H.P.V., 2018, Kinase-targeted cancer therapies: progress, challenges and future directions, Mol. Cancer, 17, 48. CrossRef

Castro-Alvarez, A., Costa, A.M. and Vilarrasa, J., 2017, The Performance of Several Docking Programs at Reproducing Protein-Macrolide-Like Crystal Structures, Molecules, 22(1), E136. CrossRef

Ferreira, L.G., dos Santos, R.N., Oliva, G. and Andricopulo, A.D., 2015, Molecular docking and structure-based drug design strategies, Molecules, 20(7), 13384-13421. CrossRef

Forli, S., 2015, Charting a Path to Success in Virtual Screening, Molecules, 20(10), 18732-18758. CrossRef

Forli, S., Huey, R., Pique, M.E., Sanner, M., Goodsell, D.S. and Olson, A.J., 2016, Computational protein-ligand docking and virtual drug screening with the AutoDock suite, Nat. Protoc., 11(5), 905-919. CrossRef

Ginovyan, M., Petrosyan, M. and Trchounian, A., 2017, Antimicrobial activity of some plant materials used in Armenian traditional medicine, BMC Complement. Altern. Med., 17, 50. CrossRef

Gupta, D., Gupta, S.V., Lee, K.D. and Amidon, G.L., 2009, Chemical and enzymatic stability of amino acid prodrugs containing methoxy, ethoxy and propylene glycol linkers, Mol. Pharm., 6(5), 1604-1611. CrossRef

Haryanti, S. and Widiyastuti, Y., 2017, Aktivitas Sitotoksik pada Sel MCF-7 dari Tumbuhan Indonesia untuk Pengobatan Tradisional Kanker Payudara, Media Penelitian Pengembangan Kesehatan, 27(4), 247-254. CrossRef

Khan, A.Y. and Kumar, G.S., 2015, Natural isoquinoline alkaloids: binding aspects to functional proteins, serum albumins, hemoglobin, and lysozyme, Biophys. Rev., 7(4), 407-420. CrossRef

Long, J., Song, J., Zhong, L., Liao, Y., Liu, L. and Li, X., 2019, Palmatine: A review of its pharmacology, toxicity and pharmacokinetics, Biochimie, 162, 176-184. CrossRef

Lu, J.J., Bao, J.L., Chen, X.P., Huang, M. and Wang, Y.T., 2012, Alkaloids Isolated from Natural Herbs as the Anticancer Agents, Evid. Based Complement. Alternat. Med., 2012, 485042. CrossRef

Luscombe, N.M., Laskowski, R.A. and Thornton, J.M., 2001, Amino acid–base interactions: a three-dimensional analysis of protein–DNA interactions at an atomic level, Nucleic Acids Res., 29(13), 2860-2874. CrossRef

Mahavorasirikul, W., Viyanant, V., Chaijaroenkul, W., Itharat, A. and Na-Bangchang, K., 2010, Cytotoxic activity of Thai medicinal plants against human cholangiocarcinoma, laryngeal and hepatocarcinoma cells in vitro, BMC Complement. Altern. Med., 10, 55. CrossRef

Megantara, S., Iwo, M.I., Levita, J. and Ibrahim, S., 2016, Determination of ligand position in aspartic proteases by correlating Tanimoto coefficient and binding affinity with root mean square deviation, J. Appl. Pharm. Sci., 6(1), 125-129. CrossRef

Morris, G.M., Huey, R., Lindstrom, W., Sanner, M.F., Belew, R.K., Goodsell, D.S. and Olson, A.J., 2009, AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility, J. Comput. Chem., 30(16), 2785-2791. CrossRef

Natesan, S., Subramaniam, R., Bergeron, C. and Balaz, S., 2012, Binding affinity prediction for ligands and receptors forming tautomers and ionization species: inhibition of mitogen-activated protein kinase-activated protein kinase 2 (MK2), J. Med. Chem., 55(5), 2035-2047. CrossRef

Neag, M.A., Mocan, A., Echeverria, J., Pop, R.M., Bosca, C.I., Crisan, G. and Buzoianu, A.D., 2018, Berberine: Botanical Occurrence, Traditional Uses, Extraction Methods, and Relevance in Cardiovascular, Metabolic, Hepatic, and Renal Disorders, Front. Pharmacol., 9, 557. CrossRef

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

Pagadala, N.S., Syed, K. and Tuszynski, J., 2017, Software for molecular docking: a review, Biophys. Rev., 9(2), 91-102. CrossRef

Papi, F., Ferraroni, M., Rigo, R., da Ros, S., Bazzicalupi, C., Sissi, C. and Gratteri, P., 2017, Role of the Benzodioxole Group in the Interactions between the Natural Alkaloids Chelerythrine and Coptisine and the Human Telomeric G-Quadruplex DNA. A Multiapproach Investigation, J. Nat. Prod., 80(12), 3128-3135. CrossRef

Pettersen, E.F., Goddard, T.D., Huang, C.C., Couch, G.S., Greenblatt, D.M., Meng, E.C. and Ferrin, T.E., 2004, UCSF Chimera--a visualization system for exploratory research and analysis, J. Comput. Chem., 25(13), 1605-1612. CrossRef

Pratama, M.R.F., 2016, Akar Kuning (Arcangelisia flava) sebagai Inhibitor EGFR: Kajian In Silico, Jurnal Farmagazine, 3(1), 6-16.

Pratama, M.R.F. and Pratomo, G.S., 2017, Pharmacophore Optimization of Berberine as HER2 Inhibitor, Jurnal Farmasi Indonesia, 14(2), 109-117. CrossRef

Pratama, M.R.F., Suratno, S. and Mulyani, E., 2018, Antibacterial Activity of Akar Kuning (Arcangelisia flava) Secondary Metabolites: Molecular Docking Approach, Asian. J. Pharm. Clin. Res., 11(11), 447-451. CrossRef

Pratama, M.R.F. and Sutomo, S., 2018, Chemical Structure Optimization of Lupeol as ER-Α and HER2 Inhibitor, Asian. J. Pharm. Clin. Res., 11(6), 298-303. CrossRef

Qiu, H., Sun, S., Ma, X., Cui, C., Chen, G., Liu, Z., Li, H. and Liu, M., 2018, Jatrorrhizine Hydrochloride Suppresses Proliferation, Migration, and Secretion of Synoviocytes In Vitro and Ameliorates Rat Models of Rheumatoid Arthritis In Vivo, Int. J. Mol. Sci., 19(5), E1514. CrossRef

Rad, S.Z.K., Rameshrad, M. and Hosseinzadeh, H., 2017, Toxicology effects of Berberis vulgaris (barberry) and its active constituent, berberine: a review, Iran. J. Basic Med. Sci., 20(5), 516-529. CrossRef

Ramirez, D. and Caballero, J., 2018, Is It Reliable to Take the Molecular Docking Top Scoring Position as the Best Solution without Considering Available Structural Data?, Molecules, 23(5), 1038. CrossRef

Ravindranath, P.A., Forli, S., Goodsell, D.S., Olson, A.J. and Sanner, M.F., 2015, AutoDockFR: advances in protein-ligand docking with explicitly specified binding site flexibility, PLOS Comput. Biol., 11(12), e1004586. CrossRef

Sicheri, F., Moarefi, I. and Kuriyan, J., 1997, Crystal structure of the Src family tyrosine kinase Hck, Nature, 385(6617), 602-609. CrossRef

Singh, H., Srivastava, H.K. and Raghava, G.P.S., 2016, A web server for analysis, comparison and prediction of protein ligand binding sites, Biol. Direct., 11, 14. CrossRef

Talpaz, M., Saglio, G., Atallah, E. and Rousselot, P., 2018, Dasatinib dose management for the treatment of chronic myeloid leukemia, Cancer, 124(8), 1660-1672. CrossRef

Trott, O. and Olson, A.J., 2010, AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization and multithreading, J. Comput. Chem., 31(2), 455-461. CrossRef

Wee, P. and Wang, Z., 2017, Epidermal Growth Factor Receptor Cell Proliferation Signaling Pathways, Cancers,, 9(5), 52. CrossRef

Yi, F., Li, L., Xu, L.J., Meng, H., Dong, Y.M., Liu, H.B. and Xiao, P.G., 2018, In silico approach in reveal traditional medicine plants pharmacological material basis, Chin. Med., 13, 33. CrossRef

Yuan, S., Chan, S. and Hu, Z., 2017, Using PyMOL as a platform for computational drug design, Wiley Interdiscip. Rev. Comput. Mol. Sci., 7(2), e1298. CrossRef


Copyright (c) 2019 Indonesian Journal of Cancer Chemoprevention

Indexed by:




Indonesian Society for Cancer Chemoprevention