In silico study of potential alkaloid compounds in Kratom Leaves (Mitragyna speciosa) as CNS stimulant
DOI:
10.29303/sjp.v7i2.685Downloads
Abstract
Dysfunction of Central Nervous System (CNS) is often associated with various neurological and psychiatric disorders. The use of stimulant can improve CNS function. Kratom leaves (Mitragyna speciosa) are predicted to have potential as CNS stimulant candidate through the inhibition of dopamine transporter (DAT) receptor. The objective of this study is to determine potential of alkaloid compounds contained in kratom leaves as CNS stimulant using in silico approach. This study was conducted in silico through the prediction of physicochemical properties (SwissADME), pharmacokinetic profiles (pkCSM), and molecular docking. The target protein used for DAT receptor was SLC6A3 with PDB ID: 8Y2C and 9EO4. The results showed that five test compounds met Lipinski’s Rule of Five. Pharmacokinetic predictions show that five test compounds have good pharmacokinetic profiles, with favorable absorption and distribution, although some compounds have potential to cause drug interactions and certain toxicities. Mitragynine, Paynantheine, Speciogynine, and Speciociliatine, have potential as CNS stimulants by inhibiting the DAT receptor, with binding energies ranging from -6,2 to -8,3 kcal/mol. Four of the five alkaloids in kratom leaves are predicted to have potential as CNS stimulants by inhibiting DAT receptors in silico.
Keywords:
Stimulant, DAT, Kratom (Mitragyna speciosa), In Silico, DockingReferences
Al-Mohaya, M., Mesut, B., Kurt, A., & Çelik, Y. S. (2024). In silico approaches which are used in pharmacy. Journal of Applied Pharmaceutical Science, 14(4), 225–239. https://doi.org/10.7324/JAPS.2024.154854
Amrulloh, L., Harmastuti, N., Prasetiyo, A., & Herowati, R. (2023). Analysis of molecular docking and dynamics simulation of mahogany (Swietenia macrophylla King) compounds against the PLpro enzyme SARS-COV-2. Jurnal Farmasi Dan Ilmu Kefarmasian Indonesia, 10(3), 347–359.
Az-Zahra, F., Afidika, J., Diamantha, S. D. A., Rahmani, A. E., Fatimah, S., Aulifa, D. L., Elaine, A. A., & Sitinjak, B. D. P. (2022). In silico study of betel leaves compound (Piper betle L.) as acetylcholinesterase (AChE) enzyme inhibitor in alzheimer disease. Vol, 2, 44–58.
Buttenschoen, M., Morris, G. M., & Deane, C. M. (2024). PoseBusters: AI-based docking methods fail to generate physically valid poses or generalise to novel sequences. Chem. Sci., 15(9), 3130–3139. https://doi.org/10.1039/D3SC04185A
Darianudin, D., Wilapangga, A., Noordam, E. R., Pramudiyawati, A., & Putri, D. E. (2026). Evaluasi Komprehensif Drug-Likeness, Profil ADMET, dan Potensi Bioavailabilitas Dua Polimetoksiflavon Citrus Menggunakan Pendekatan In Silico. Jurnal Fitofarmaka Dan Kesehatan, 2(2).
Dastmalchi, S., Hamzeh-Mivehroud, M., & Sokouti, B. (2016). Methods and algorithms for molecular docking-based drug design and discovery. IGI Global.
Esteves, F., Rueff, J., & Kranendonk, M. (2021). The central role of cytochrome P450 in xenobiotic metabolism—a brief review on a fascinating enzyme family. Journal of Xenobiotics, 11(3), 94–114.
Firmansyah, A., Sundalian, M., & Taufiq, M. (2021). Kratom (Mitragyna speciosa korth) for a new medicinal: A review of pharmacological and compound analysis. Biointerface Research in Applied Chemistry, 11(2), 9704–9718.
Herdini, H. (2023). Studi In Silico: Senyawa Aktif Akar Senggugu (Clerodendrum serratum) terhadap Penghambatan Reseptor Human Chitotriosidase-1 (hCHIT1) sebagai Antiasma. Sainstech: Jurnal Penelitian Dan Pengkajian Sains Dan Teknologi, 33(2), 91–107.
Hospital, C., Wang, X., Meng, Y., & Hu, T. (2024). Dopamine reuptake and inhibitory mechanisms in human dopamine transporter. March. https://doi.org/10.1038/s41586-024-07796-0
Inayah, I., Hadisoebroto, G., & Aini, F. N. (2024). Studi In Silico Senyawa dari Herba Sambiloto (Andrographis paniculata) terhadap Protein Dihydrofolate Reductase (4KM2) pada Mycobacterium tuberculosis. Jurnal Sabdariffarma: Jurnal Ilmiah Farmasi, 12(1), 32–50.
Kruegel, A. C., & Grundmann, O. (2018). The medicinal chemistry and neuropharmacology of kratom: A preliminary discussion of a promising medicinal plant and analysis of its potential for abuse. Neuropharmacology, 134, 108–120. https://doi.org/https://doi.org/10.1016/j.neuropharm.2017.08.026
Makisake, R. G., Montolalu, R. I., Mewengkang, H. W., Sanger, G., Harikedua, S. D., Makapedua, D. M., Salindeho, N., Zagoto, E. B. S., & Gumolung, I. (2022). Studi In Silico Senyawa Aktif Daun Tagalolo (Ficus septica Burm F) sebagai Ligan Uji pada Enzim L-Histidin Decarboxylase. Media Teknologi Hasil Perikanan, 10(2), 122–126.
Mardianingrum, R., Bachtiar, K. R., Susanti, S., Nuraisah, A. N. A., & Ruswanto, R. (2021). Studi in silico senyawa 1, 4-Naphthalenedione-2-Ethyl-3-Hydroxy sebagai antiinflamasi dan antikanker payudara. ALCHEMY Jurnal Penelitian Kimia, 17(1), 83–95.
Mastura, E. Y., Asri, M. T., & Purnama, E. R. (2020). Biokomputasi Aktivitas Senyawa D-alpha-Tocopherol dari Ekstrak Daun Zodia (Evodia suaveolens) sebagai Antikanker secara In Silico. LenteraBio: Berkala Ilmiah Biologi, 9(2), 129–136.
Muslikh, F. A., Nahdhia, N., Susilawati, D., Sari, F., Nugroho, S., Werdiningsih, W., & Basuki, D. (2025). Prediksi Druglikeness Dan Potensi Aktivitas Biologis Senyawa Metabolit Sekunder Daun Asam Jawa (Tamarindus indica). Jurnal Sintesis: Penelitian Sains, Terapan Dan Analisisnya.
Nasution, M. A., Gultom, N., & Silitonga, M. (2025). Literatur Review: Kajian Tanaman Obat Untuk Mengatasi Penyakit Sistem Saraf Pusat di Indonesia. Symbiotic: Journal of Biological Education and Science, 6(1), 32–44. https://doi.org/10.32939/symbiotic.v6i1.167
Nepal, B., Das, S., Reith, M. E., & Kortagere, S. (2023). Overview of the structure and function of the dopamine transporter and its protein interactions. Frontiers in Physiology, Volume 14. https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2023.1150355
Newman, A. H., Ku, T., Jordan, C. J., Bonifazi, A., & Xi, Z.-X. (2021). New Drugs, Old Targets: Tweaking the Dopamine System to Treat Psychostimulant Use Disorders. Annual Review of Pharmacology and Toxicology, 61, 609–628. https://doi.org/10.1146/annurev-pharmtox-030220-124205
Nielsen, J. C., Salomon, K., Kalenderoglou, I. E., Bargmeyer, S., Pape, T., Shahsavar, A., & Loland, C. J. (2024). Structure of the human dopamine transporter in complex with cocaine. 632(March). https://doi.org/10.1038/s41586-024-07804-3
Nofianti, K. A., Hakim, L., Suzana, S., & Ifadotunnikmah, F. (2024). Prediction of the Potential of Benzoxazinone, 2-phenyl-4H-benzo [1, 3] oxazin-4-one, and 2-[2-(4-methoxyphenyl) vinyl]-3, 1-benzoxazin-4-one as New Anti-Tuberculosis.
Nursanti, O. (2021). Validasi Penambatan Molekul Untuk Mendapatkan Ligan Aktif Pada Reseptor Cyclooxygenase 2. Prosiding Seminar Informasi Kesehatan Nasional, 411–430.
Nursanti, O. (2023). Prediksi Toksisitas Dan Farmakokinetika Untuk Mendapatkan Kandidat Obat Antidiabetes: Prediksi Toksisitas Dan Farmakokinetika Untuk Mendapatkan Kandidat Obat Antidiabetes. Journal Pharmaceutical Care and Sciences, 3(2), 1–9.
Oktaviani, T., Hermansyah, O., Ikhsan, I., Rahmawati, S., & Wirahmi, N. (2024). Docking Molecular Senyawa Pada Tanaman Famili Apiaceae Sebagai Penghambat Enzim Xanthine Oxidase. Jurnal Farmasi Higea, 16(1), 34–42.
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.
Pramudiyawati, A., Putri, D. E., Nurfadilah, N., & Wilapangga, A. (2024). Skrining studi in silico potensi farmakokinetika dan toksisitas senyawa 6, 10, 14-trimetil-2-pentadekanon dari ekstrak daun ekaliptus. Indonesian Journal of Pharmaceutical Education, 4(1).
Prasetio, A. (2020). Gangguan Psikiatri Terkait Kafein. Cermin Dunia Kedokteran, 47(7), 378. https://doi.org/10.55175/cdk.v47i7.603
Purnaningtyas, S. R. D., & Andaririt, D. R. (2025). Molecular Docking Of Quercetin As An Anti-Breast Cancer Agent. Open Access Health Scientific Journal, 6(2 SE-Articles), 342–350. https://doi.org/10.55700/oahsj.v6i2.126
Rahmi, M., Tobat, S. R., & Ningsih, S. (2018). Uji efek stimulan sistem saraf pusat ekstrak etanol daun Afrika Selatan (Vernonia amygdalina delile) pada mencit putih betina. Scientia J. Far. Kes., 8(2), 137–143. https://doi.org/10.48191/medfarm.v9i2.35
Reith, M. E. A., Kortagere, S., Wiers, C. E., Sun, H., Kurian, M. A., Galli, A., Volkow, N. D., & Lin, Z. (2022). The dopamine transporter gene SLC6A3: multidisease risks. Molecular Psychiatry, 27(2), 1031–1046.
Saputra, A., Wientarsih, I., Sutardi, L. N., Rafi, M., & Mariya, S. (2024). Penambatan Molekuler Senyawa Bioaktif Tanaman Metang terhadap Reseptor Estrogen Alfa sebagai Antikanker. Acta VETERINARIA Indonesiana, 12(3), 203–210.
Sari, S. W., Wilapangga, A., Sari, A. N., & Astriani, S. (2023). STUDI IN SILICO POTENSI FARMAKOKINETIK DUA SENYAWA DARI TANAMAN KENAF (Hibiscus cannabinus L) UNTUK PREDIKSI TOKSISITAS. Jurnal Bina Cipta Husada: Jurnal Kesehatan Dan Science, 19(2), 70–79.
Scott, O. B., Gu, J., & Chan, A. W. E. (2022). Classification of Protein-Binding Sites Using a Spherical Convolutional Neural Network. Journal of Chemical Information and Modeling, 62(22), 5383–5396. https://doi.org/10.1021/acs.jcim.2c00832
Sofia, N., Yuniarti, Y., & Rosidah, R. (2022). UJI FITOKIMIA TERHADAP TANAMAN OBAT KRATOM (Mitragyna speciosa) DI KHDTK ULM. Jurnal Sylva Scienteae, 5(2), 218. https://doi.org/10.20527/jss.v5i2.5356
Suliasih, B. A., & Mun’im, A. (2022). Review: Potensi dan Masalah dalam Pengembangan Kemandirian Bahan Baku Obat Tradisional di Indonesia. Chemistry and Materials, 1(1), 28–33. https://doi.org/10.56425/cma.v1i1.22
Tahir, M. (2024). STUDI IN SILICO SENYAWA AKTIF DARI JAHE (Zingiber officinale) DAN KERSEN (Muntingia calabura L.) SEBAGAI INHIBITOR MAIN PROTEASE (Mpro) DARI SARS-CoV-2. As-Syifaa Jurnal Farmasi, 16(1), 35–44.
Wibisono, N., & Martino, Y. A. (2023). Uji aktivitas antidiabetes kulit batang pulai (alstonia scholaris) melalui studi in silico dan prediksi profil farmakokinetika. Jurnal Ilmiah Biosaintropis (Bioscience-Tropic), 8(2), 59–64.
Wilapangga, A., & Arif, M. (2025). Analisis Prediksi Potensi Farmakokinetik Dan Toksisitas Pada Senyawa Kurkumin Dari Extrak Curcuma Aromatica Secara In Silico. The Journal Of Pharmacy, 2(2), 156–165.
Wilapangga, A., Kurnia, N., Mahroji, M., & Hidayat, A. (2025). Prediksi Profil Farmakokinetik dan Toksisitas Senyawa Aktif Ekstrak Daun Kratom ( Mitragyna speciosa ) Secara In Silico Menggunakan pkCSM dan SwissADME. Journal Of Pharmacy UMRI, 2(2), 174–180.
Wulandari, R. P., Gabriel, K., Nurdin, H. A., Pakhrul, D. H. F., Harits, S. S., Prameswari, N., Pribadi, A. P. A., & Aulifa, D. L. (2023). In silico study of secondary metabolite compounds in parsley (Petroselinum crispum) as a drug therapy for blood cancer (myeloproliferative neoplasm (MPN)) targeting JAK-2. Indonesian Journal of Chemical Science, 12(2), 212–224.
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