EVALUASI IN SILICO KAEMPFEROL SEBAGAI POTENSIAL INHIBITOR TIROSINASE : MOLECULAR DOCKING DAN PREDIKSI ADMET
DOI:
https://doi.org/10.31004/jkt.v6i4.50623Keywords:
ADMET, flavonoid, hiperpigmentasi, kaempferol, molecular docking, tirosinaseAbstract
Tirosinase merupakan enzim kunci dalam biosintesis melanin, dan aktivitasnya yang berlebihan berperan penting dalam terjadinya gangguan hiperpigmentasi kulit seperti melasma, freckles, dan bintik penuaan. Penggunaan inhibitor tirosinase sintetis seperti hidrokuinon dan asam kojat sering menimbulkan efek samping, sehingga diperlukan alternatif alami yang lebih aman. Kaempferol, suatu flavonoid yang banyak ditemukan pada tanaman seperti Moringa oleifera, dilaporkan memiliki aktivitas antioksidan dan potensi penghambatan enzim. Penelitian ini bertujuan mengevaluasi potensi kaempferol sebagai inhibitor tirosinase melalui pendekatan in silico menggunakan analisis molecular docking dan prediksi ADMET. Struktur tiga dimensi kaempferol diperoleh dari basis data PubChem, sedangkan protein tirosinase (PDB ID: 5M8L) diunduh dari Protein Data Bank. Proses docking dilakukan dengan CB-Dock2 berbasis AutoDock Vina, sedangkan analisis farmakokinetik dan toksisitas dilakukan menggunakan SwissADME dan pkCSM. Hasil menunjukkan bahwa kaempferol memiliki afinitas ikatan kuat terhadap situs aktif tirosinase dengan skor –9,1 kcal/mol, serta membentuk interaksi hidrogen dan hidrofobik stabil dengan residu kunci His, Phe, dan Glu. Prediksi ADMET mengindikasikan kaempferol memiliki absorpsi usus tinggi (74,29%), distribusi yang baik, serta toksisitas rendah tanpa indikasi hepatotoksik maupun kardiotoksik. Berdasarkan hasil ini, kaempferol dinilai berpotensi sebagai kandidat utama inhibitor tirosinase alami yang aman dan efektif. Studi lanjutan in vitro dan in vivo diperlukan untuk memvalidasi potensi terapeutik dan kosmetiknya.References
Calderón-Montaño, J. M., Burgos-Morón, E., Pérez-Guerrero, C., & López-Lázaro, M. (2011). A Review on the Dietary Flavonoid Kaempferol | BenthamScience. Mini Reviews in Medicinal Chemistry, 11(4), 298–344. http://www.eurekaselect.com/87782/article%5Cnhttp://personal.us.es/mlopezlazaro/2011. MRMC. Kaempferol.pdf%5Cnhttp://www.ncbi.nlm.nih.gov/pubmed/21428901
Chang, T. S. (2009). An updated review of tyrosinase inhibitors. International Journal of Molecular Sciences, 10(6), 2440–2475. https://doi.org/10.3390/ijms10062440
d’Ischia, M., Wakamatsu, K., Cicoira, F., Di Mauro, E., Garcia-Borron, J. C., Commo, S., Galván, I., Ghanem, G., Kenzo, K., Meredith, P., Pezzella, A., Santato, C., Sarna, T., Simon, J. D., Zecca, L., Zucca, F. A., Napolitano, A., & Ito, S. (2015). Melanins and melanogenesis: From pigment cells to human health and technological applications. Pigment Cell and Melanoma Research, 28(5), 520–544. https://doi.org/10.1111/pcmr.12393
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(July), 226–233. https://doi.org/10.1016/j.foodres.2017.07.010
Hassan, M., Shahzadi, S., & Kloczkowski, A. (2023). Tyrosinase Inhibitors Naturally Present in Plants and Synthetic Modifications of These Natural Products as Anti-Melanogenic Agents: A Review. Molecules, 28(1). https://doi.org/10.3390/molecules28010378
Jakimiuk, K., Sari, S., Milewski, R., Supuran, C. T., Şöhretoğlu, D., & Tomczyk, M. (2022). Flavonoids as tyrosinase inhibitors in in silico and in vitro models: basic framework of SAR using a statistical modelling approach. Journal of Enzyme Inhibition and Medicinal Chemistry, 37(1), 421–430. https://doi.org/10.1080/14756366.2021.2014832
Kim, J. H., Cho, I. S., So, Y. K., Kim, H. H., & Kim, Y. H. (2018). Kushenol A and 8-prenylkaempferol, tyrosinase inhibitors, derived from Sophora flavescens. Journal of Enzyme Inhibition and Medicinal Chemistry, 33(1), 1048–1054. https://doi.org/10.1080/14756366.2018.1477776
Krajewska, A., Oniszczuk, T., Polak, B., & Oniszczuk, A. (2025). Hepatoprotective Effect of Kaempferol — A Review. 1–21.
Li, X., Guo, J., Lian, J., Gao, F., Khan, A. J., Wang, T., & Zhang, F. (2021). Molecular Simulation Study on the Interaction between Tyrosinase and Flavonoids from Sea Buckthorn. ACS Omega, 6(33), 21579–21585. https://doi.org/10.1021/acsomega.1c02593
Limtrakul, P., Khantamat, O., & Pintha, K. (2005). Inhibition of P-glycoprotein function and expression by kaempferol and quercetin. Journal of Chemotherapy, 17(1), 86–95. https://doi.org/10.1179/joc.2005.17.1.86
Lipinski, C. A., Lombardo, F., Dominy, B. W., & Feeney, P. J. (2012). Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Advanced Drug Delivery Reviews, 64(SUPPL.), 4–17. https://doi.org/10.1016/j.addr.2012.09.019
Ma, Y., Zhang, C., Li, J., Xiong, J., & Xiao, B. L. (2024). Inhibitory mechanism on tyrosinase activity of flavonoids from flower buds of Sophora japonica L. Heliyon, 10(19), e38252. https://doi.org/10.1016/j.heliyon.2024.e38252
Obaid, R. J., Mughal, E. U., Naeem, N., Sadiq, A., Alsantali, R. I., Jassas, R. S., Moussa, Z., & Ahmed, S. A. (2021). Natural and synthetic flavonoid derivatives as new potential tyrosinase inhibitors: a systematic review. RSC Advances, 11(36), 22159–22198. https://doi.org/10.1039/d1ra03196a
Parvez, S., Kang, M., Chung, H.-S., Cho, C., Hong, M.-C., Shin, M.-K., & Bae, H. (2006). Survey and Mechanism of Skin Depigmenting and Lightening Agents. Phytotherapy Research, 20, 921–934. https://doi.org/10.1002/ptr
Pires, D. E. V., Blundell, T. L., & Ascher, D. B. (2015). pkCSM: Predicting small-molecule pharmacokinetic and toxicity properties using graph-based signatures. Journal of Medicinal Chemistry, 58(9), 4066–4072. https://doi.org/10.1021/acs.jmedchem.5b00104
PubChem. (2025). Kaempferol. https://pubchem.ncbi.nlm.nih.gov/compound/5280863
Siddhuraju, P., & Becker, K. (2003). Antioxidant properties of various solvent extracts of total phenolic constituents from three different agroclimatic origins of drumstick tree (Moringa oleifera Lam.) leaves. Journal of Agricultural and Food Chemistry, 51(8), 2144–2155. https://doi.org/10.1021/jf020444+
Siridechakorn, I., Pimpa, J., Choodej, S., Ngamrojanavanich, N., & Pudhom, K. (2023). Synergistic impact of arbutin and kaempferol-7-O-α-l-rhamnopyranoside from Nephelium lappaceum L. on whitening efficacy and stability of cosmetic formulations. Scientific Reports, 13(1), 1–9. https://doi.org/10.1038/s41598-023-49351-3
Solano, F. (2017). Melanin and melanin-related polymers as materials with biomedical and biotechnological applications— Cuttlefish ink and mussel foot proteins as inspired biomolecules. International Journal of Molecular Sciences, 18(7). https://doi.org/10.3390/ijms18071561
Wojtasek, H. (2022). Comment on “Natural and synthetic flavonoid derivatives as new potential tyrosinase inhibitors: a systematic review” by R. Obaid, E. Mughal, N. Naeem, A. Sadiq, R. Alsantali, R. Jassas, Z. Moussa and S. Ahmed, RSC Advances, 2021, 11, 22159. RSC Advances, 12(9), 5395–5397. https://doi.org/10.1039/d1ra08162d
Xing, F., Wang, Z., Bahadar, N., Wang, C., & Wang, X. D. (2024). Molecular insights into kaempferol derivatives as potential inhibitors for CDK2 in colon cancer: pharmacophore modeling, docking, and dynamic analysis. Frontiers in Chemistry, 12(August). https://doi.org/10.3389/fchem.2024.1440196
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
Downloads
Published
Issue
Section
License
Copyright (c) 2025 Rhea Nugraha
This work is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work’s authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal’s published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).
