Studi Docking Molekular Aktivitas Panghambatan Enzim Tirosinase Ubi Jalar (Ipomoea batatas L. Lam)

Dwi Utami(1*), Ryan Syahputra(2), Wahyu Widyaningsih(3)

(1) Universitas Ahmad Dahlan
(2) Universitas Ahmad Dahlan
(3) Universitas Ahmad Dahlan
(*) Corresponding Author

Abstract

Sweet potato (Ipomoea batatas L. Lam) is a plant source of carbohydrates with chemical content of catechins, quercetin, asam klorogenat, anthocyanins, beta-carotene. These phytochemical compounds have been shown to have antioxidant activity that is closely related to tyrosinase through the oxidative stress pathway. The purpose of this study was to develop sweet potato plants as anti-tyrosinase candidates for cosmetic preparations by molecular docking of these 4 compounds to tyrosinase protein (pdb:2Y9X) with kojic acid control. The research was done in 4 stages : (1) Preparation of proteins (receptors) and ligands with Biovia Discovery Studio (2) Optimization of geometry with Avogadro and Chem 3D (3) Validation of docking and molecular docking methods for proteins (2Y9X) with Autodock-4 (5) and (4) ADMET study with pkCSM and SwissADME websites. The test results obtained the highest affinity for 3 active compounds, namely beta-carotene with (ΔG) -6.05 kcal/mol (IC) 36.72 M and quercetin has (ΔG) -5.87 kcal/mol (IC) 45.30 M . While the control kojic acid has a lower affinity of (ΔG) -5.27 kcal/mol (IC) 380.37 M. ADMET predictions provide information that the four active compounds Ipomoea batatas L. Lam meet the requirements to be developed as natural tyrosinase inhibitors based on lipophilicity (logP), topology polar surface area (TPSA), skin permeability, skin sensitivity, logKP, CYP1A2 inhibitor, lipinski rule. and bioavailability. The molecular docking study and ADMET prediction indicate that the active compound of sweet potato (Ipomoea batatas L. Lam) has the potential to be developed as a natural cosmetic ingredient.

Keywords

Tyrosinase, Ipomoea batatas L. Lam, protein (pdb:2Y9X), Molecular docking, Autodock-4

Full Text:

PDF

References

Allouche, A. (2012). Software News and Updates Gabedit - A Graphical User Interface for Computational Chemistry Softwares. Journal of Computational Chemistry, 32, 174-182. https://doi.org/10.1002/jcc.

Bae, J. Y., Lim, S. S., Kim, S. J., Choi, J. S., Park, J., Ju, S. M., Han, S. J., Kang, I. J., & Kang, Y. H. (2009). Bog blueberry anthocyanins alleviate photoaging in ultraviolet-B irradiation-induced human dermal fibroblasts. Molecular Nutrition and Food Research, 53(6), 726–738. https://doi.org/10.1002/mnfr.200800245.

Clifford, I. O., Kingsley, E., Chika, C. O., & Chinyere, I. I. (2014). Effects of Osmotic Dewatering and Oven Drying on β-Carotene Content of Sliced Light Yellow-Fleshed Sweet Potato (Ipomea batatas L.). Nigerian Food Journal, 32(2), 25-32. https://doi.org/10.1016/s0189-7241(15) 30114-4

Eluagu Ester, (2010). Effect of blanching on the mineral composition and antinutritional factors. 124-128.

Fan, M., Zhang, G., Hu, X., Xu, X., & Gong, D. (2017). Quercetin as a tyrosinase inhibitor: Inhibitory activity, conformational change and mechanism. Food Research International, 100 (April), 226-233. https://doi.org/10.1016/j.foodres.2017.07.010

Girija, C. R., Karunakar, P., Poojari, C. S., Begum, N. S., & Syed, A. A. (2010). Molecular docking studies of curcumin derivatives with multiple protein targets for procarcinogen activating enzyme inhibition. Journal of Proteomics and Bioinformatics, 3(6), 200–203. https://doi.org/10.4172/jpb.1000140

Harwansh, R. K., Mukherjee, P. K., Kar, A., Bahadur, S., Al-Dhabi, N. A., & Duraipandiyan, V. (2016). Enhancement of photoprotection potential of catechin loaded nanoemulsion gel against UVA induced oxidative stress. Journal of Photochemistry and Photobiology B: Biology, 160, 318–329. https://doi.org/10.1016/j.jphotobiol.2016.03.026

Huang, S., Ren, Y., Peng, X., Qian, P., & Meng, L. (2019). Computer-aid drug design, synthesis, and anticoagulant activity evaluation of novel dabigatran derivatives as thrombin inhibitors. European Journal of Pharmaceutical Sciences, 137(April), 104965. https://doi.org/10.1016/j.ejps.2019.104965

Isemura, M. (2019). Catechin in human health and disease. Molecules, 24(3). https://doi.org/10.3390/ molecules 24030528

Islam, M. S., Jalaluddin, M., Garner, J. O., Yoshimoto, M., & Yamakawa, O. (2005). Artificial shading and temperature influence on anthocyanin compositions in sweetpotato leaves. Hort Science, 40 (1), 176-180. https : // doi. org / 10.21273/ hortsci. 40.1.176

Islam, S. (2016). Some Bioactive Constituents, Antioxidant, and Antimutagenic Activities in the Leaves of Ipomoea batatas Lam. Genotypes. American Journal of Food Science and Technology, Vol. 4, 2016, Pages 70-80, 4(3), 70–80. https://doi.org/10.12691/ajfst-4-3-3

Ismaya, W. T., Rozeboom, J., Weijn, A., Mes, J. J., & Fusetti, F. (2011). Crystal Structure of Agaricus bisporus Tyrosinase. Biochemistry, 50, 5477-5486.

Jain, A. N., & Nicholls, A. (2008). Recommendations for evaluation of computational methods. Journal of Computer-Aided Molecular Design, 22(3-4), 133-139. https://doi.org/10.1007/ s10822-008-9196-5

Jiang, Y., Akhavan Aghdam, Z., Tsimring, L. S., & Hao, N. (2017). Coupled feedback loops control the stimulus-dependent dynamics of the yeast transcription factor Msn2. Journal of Biological Chemistry, 292(30), 12366–12372. https : // doi. org/ 10. 1074/ jbc. C117. 800896

Kho, K., Sim, Y. Y., & Nyam, K. L. (2019). Antioxidant activities of tea prepared from kenaf (Hibiscus cannabinus L. KR9) leaves at different maturity stages. Journal of Food Measurement and Characterization, 13(3), 2009–2016. https://doi.org/10.1007/s11694-019-00121-8

Kontoyianni, M., McClellan, L. M., & Sokol, G. S. (2004). Evaluation of Docking Performance: Comparative Data on Docking Algorithms. Journal of Medicinal Chemistry, 47(3), 558-565. https : // doi. org / 10.1021/ jm0302997

Lai, X., Wichers, H. J., Soler-Lopez, M., & Dijkstra, B. W. (2017). Structure of Human Tyrosinase Related Protein 1 Reveals a Binuclear Zinc Active Site Important for Melanogenesis. Angewandte Chemie - International Edition, 56(33), 9812–9815. https://doi.org/10.1002/anie.201704616

Masaki, H. (2010). Role of antioxidants in the skin: Anti-aging effects. Journal of Dermatological Science, 58(2), 85–90. https://doi.org/10.1016/j.jdermsci.2010.03.003

Mohanraj, R., & Sivasankar, S. (2014). Sweet potato (Ipomoea batatas [L.] Lam) - A valuable medicinal food: A review. Journal of Medicinal Food, 17(7), 733–741. https://doi.org/10.1089/jmf.2013.2818

Mukherjee, P. K., Maity, N., Nema, N. K., & Sarkar, B. K. (2011). Bioactive compounds from natural resources against skin aging. Phytomedicine, 19(1), 64–73. https://doi.org/10.1016/ j.phymed.2011.10.003

Nguyen, H. X., Nguyen, N. T., Nguyen, M. H. K., Le, T. H., Do, T. N., Hung, T. M., & Nguyen, M. T. T. (2016). Tyrosinase inhibitory activity of flavonoids from Artocarpus heterophyllous. Chemistry Central Journal, 10(1), 4–9. https://doi.org/10.1186/s13065-016-0150-7

Pinzi, L., & Rastelli, G. (2019). Molecular docking: Shifting paradigms in drug discovery. International Journal of Molecular Sciences, 20(18). https : // doi.org/ 10.3390/ ijms 20184331

Rutkowski, M., & Grzegorczyk, K. (2012). Adverse effects of antioxidative vitamins. International Journal of Occupational Medicine and Environmental Health, 25(2), 105–121. https://doi.org/10.2478/S13382-012-0022-x

Saeedi, M., Eslamifar, M., & Khezri, K. (2019). Kojic acid applications in cosmetic and pharmaceutical preparations. Biomedicine and Pharmacotherapy, 110(February), 582–593. https://doi.org/10.1016/j.biopha.2018.12.006

Singh, S. (2006). Preclinical Pharmacokinetics: An Approach Towards Safer and Efficacious Drugs. Current Drug Metabolism, 7 (2), 165-182. https://doi.org/10.2174 /138920006775541552

Woolery-Lloyd, H., & Kammer, J. N. (2011). Treatment of Hyperpigmentation. Seminars in Cutaneous Medicine and Surgery, 30(3), 171–175. https://doi.org/10.1016/j.sder.2011.06.004

Xin, J., Qi, Y., Cai, J., Feng, C., Akihisa, T., & Li, W. (2021). Phenolic compounds from Ficus hispida L . f . as tyrosinase and melanin inhibitors : Biological evaluation , molecular docking , and molecular dynamics. 1244. https://doi.org/10.1016/j. molstruc.2021.130951

Zeb, A., & Murkovic, M. (2013). Determination of thermal oxidation and oxidation products of β-carotene in corn oil triacylglycerols. Food Research International, 50(2), 534–544. https://doi.org/10.1016/j.foodres.2011.02.039

Zengin, G., Locatelli, M., Stefanucci, A., Macedonio, G., Novellino, E., Mirzaie, S., Dvorácskó, S., Carradori, S., Brunetti, L., Orlando, G., Menghini, L., Ferrante, C., Recinella, L., Chiavaroli, A., Leporini, L., & Mollica, A. (2017). Chemical characterization, antioxidant properties, anti-inflammatory activity, and enzyme inhibition of Ipomoea batatas L. leaf extracts. International Journal of Food Properties, 20(2), 1907–1919. https://doi.org/10.1080/10942912.2017.1357127

Zolghadri, S., Bahrami, A., Hassan Khan, M. T., Munoz-Munoz, J., Garcia-Molina, F., Garcia-Canovas, F., & Saboury, A. A. (2019). A comprehensive review on tyrosinase inhibitors. Journal of Enzyme Inhibition and Medicinal Chemistry, 34(1), 279–309. https://doi.org/10.1080/14756366.2018.1545767

DOI: 10.23917/pharmacon.v19i1.18295

Article Metrics

Abstract view(s): 459 time(s)
PDF: 1864 time(s)

Refbacks

  • There are currently no refbacks.