Perbandingan Prediksi Target Molekuler 7-Hidroksimitragynine dan Speciogynine Menggunakan SwissTargetPrediction: Identifikasi Target Bersama dan Target Spesifik
DOI:
https://doi.org/10.51574/illea.v2i3.6016Keywords:
7-hidroksimitraginin, speciogynine, SwissTargetPrediction, target molekuler, kratomAbstract
7-hidroksimitraginin dan speciogynine merupakan alkaloid indol dari Mitragyna speciosa (kratom) dengan kerangka struktur yang berdekatan, tetapi profil farmakologinya diduga berbeda. Penelitian ini membandingkan prediksi target molekuler kedua senyawa serta mengidentifikasi target bersama dan target spesifik masing-masing. Studi in silico deskriptif-komparatif menggunakan SwissTargetPrediction dengan organisme Homo sapiens. Seratus target teratas setiap senyawa dibandingkan berdasarkan UniProt ID, kelas target, dan nilai probabilitas. Ditemukan 20 target bersama (20%) dan masing-masing 80 target spesifik, dengan total 180 target unik (indeks Jaccard 0,11). Reseptor opioid delta (OPRD1) merupakan target berprobabilitas tertinggi pada kedua senyawa (0,439 untuk 7-hidroksimitraginin dan 0,561 untuk speciogynine). Hanya sembilan target speciogynine berprobabilitas lebih dari nol, didominasi reseptor aminergik (adrenergik α2, dopamin, serotonin) dan butirilkolinesterase, sedangkan 99 target 7-hidroksimitraginin berprobabilitas seragam rendah (0,106) dan mencakup kinase, protease, serta reseptor oreksin. Kedua senyawa memiliki irisan target yang kecil dan mengarah pada profil farmakologi yang berbeda. Hasil ini bersifat hipotesis dan memerlukan validasi eksperimental.
References
Che, T., & Roth, B. L. (2023). Molecular basis of opioid receptor signaling. Cell, 186(24), 5203–5219. https://doi.org/10.1016/j.cell.2023.10.029
Daina, A., Michielin, O., & Zoete, V. (2017). SwissADME: A free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Scientific Reports, 7(October 2016), 1–13. https://doi.org/10.1038/srep42717
Ellis, C. R., Racz, R., Kruhlak, N. L., Kim, M. T., Zakharov, A. V., Southall, N., Hawkins, E. G., Burkhart, K., Strauss, D. G., & Stavitskaya, L. (2020). Evaluating kratom alkaloids using PHASE. PLoS ONE, 15(3), 1–18. https://doi.org/10.1371/journal.pone.0229646
Gfeller, D., Grosdidier, A., Wirth, M., Daina, A., Michielin, O., & Zoete, V. (2014). SwissTargetPrediction: A web server for target prediction of bioactive small molecules. Nucleic Acids Research, 42(W1), 32–38. https://doi.org/10.1093/nar/gku293
Kamble, S. H., Sharma, A., King, T. I., Berthold, E. C., León, F., Meyer, P. K. L., Kanumuri, S. R. R., McMahon, L. R., McCurdy, C. R., & Avery, B. A. (2020). Exploration of cytochrome P450 inhibition mediated drug-drug interaction potential of kratom alkaloids. Toxicology Letters, 319, 148–154. https://doi.org/10.1016/j.toxlet.2019.11.005
Kamble, S. H., Sharma, A., King, T. I., León, F., McCurdy, C. R., & Avery, B. A. (2019). Metabolite profiling and identification of enzymes responsible for the metabolism of mitragynine, the major alkaloid of Mitragyna speciosa (kratom). Xenobiotica, 49(11), 1279–1288. https://doi.org/10.1080/00498254.2018.1552819
Kitajima, M., Misawa, K., Kogure, N., Said, I. M., Horie, S., Hatori, Y., Murayama, T., & Takayama, H. (2006). A new indole alkaloid, 7-hydroxyspeciociliatine, from the fruits of Malaysian Mitragyna speciosa and its opioid agonistic activity. Journal of Natural Medicines, 60(1), 28–35. https://doi.org/10.1007/s11418-005-0001-7
Kruegel, A. C., Gassaway, M. M., Kapoor, A., Váradi, A., Majumdar, S., Filizola, M., Javitch, J. A., & Sames, D. (2016). Synthetic and Receptor Signaling Explorations of the Mitragyna Alkaloids: Mitragynine as an Atypical Molecular Framework for Opioid Receptor Modulators. Journal of the American Chemical Society, 138(21), 6754–6764. https://doi.org/10.1021/jacs.6b00360
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. In Neuropharmacology (Vol. 134). Elsevier Ltd. https://doi.org/10.1016/j.neuropharm.2017.08.026
Matsumoto, K., Horie, S., Takayama, H., Ishikawa, H., Aimi, N., Ponglux, D., Murayama, T., & Watanabe, K. (2005). Antinociception, tolerance and withdrawal symptoms induced by 7-hydroxymitragynine, an alkaloid from the Thai medicinal herb Mitragyna speciosa. Life Sciences, 78(1), 2–7. https://doi.org/10.1016/j.lfs.2004.10.086
Obeng, S., Wilkerson, J. L., León, F., Reeves, M. E., Restrepo, L. F., Gamez-Jimenez, L. R., Patel, A., Pennington, A. E., Taylor, V. A., Ho, N. P., Braun, T., Fortner, J. D., Crowley, M. L., Williamson, M. R., Pallares, V. L. C., Mottinelli, M., Lopera-Londoño, C., McCurdy, C. R., McMahon, L. R., & Hiranita, T. (2021). Pharmacological comparison of mitragynine and 7-hydroxymitragynine: In vitro affinity and efficacy for μ-opioid receptor and opioid-like behavioral effects in rats. Journal of Pharmacology and Experimental Therapeutics, 376(3), 410–427. https://doi.org/10.1124/jpet.120.000189
Quirion, B., Bergeron, F., Blais, V., & Gendron, L. (2020). The Delta-Opioid Receptor; a Target for the Treatment of Pain. Frontiers in Molecular Neuroscience, 13(May), 1–11. https://doi.org/10.3389/fnmol.2020.00052
Sadre, R., Magallanes-Lundback, M., Pradhan, S., Salim, V., Mesberg, A., Jones, A. D., & Dellapenna, D. (2016). Metabolite diversity in alkaloid biosynthesis: A multilane (diastereomer) highway for camptothecin synthesis in camptotheca acuminata. Plant Cell, 28(8), 1926–1944. https://doi.org/10.1105/tpc.16.00193
Suhaimi, F. W., Yusoff, N. H. M., Hassan, R., Mansor, S. M., Navaratnam, V., Müller, C. P., & Hassan, Z. (2016). Neurobiology of Kratom and its main alkaloid mitragynine. Brain Research Bulletin, 126, 29–40. https://doi.org/10.1016/j.brainresbull.2016.03.015
Todd, D. A., Kellogg, J. J., Wallace, E. D., Khin, M., Flores-Bocanegra, L., Tanna, R. S., McIntosh, S., Raja, H. A., Graf, T. N., Hemby, S. E., Paine, M. F., Oberlies, N. H., & Cech, N. B. (2020). Chemical composition and biological effects of kratom (Mitragyna speciosa): In vitro studies with implications for efficacy and drug interactions. Scientific Reports, 10(1), 1–13. https://doi.org/10.1038/s41598-020-76119-w
Váradi, A., Marrone, G. F., Palmer, T. C., Narayan, A., Szabó, M. R., Le Rouzic, V., Grinnell, S. G., Subrath, J. J., Warner, E., Kalra, S., Hunkele, A., Pagirsky, J., Eans, S. O., Medina, J. M., Xu, J., Pan, Y. X., Borics, A., Pasternak, G. W., McLaughlin, J. P., & Majumdar, S. (2016). Mitragynine/Corynantheidine Pseudoindoxyls As Opioid Analgesics with Mu Agonism and Delta Antagonism, Which Do Not Recruit β-Arrestin-2. Journal of Medicinal Chemistry, 59(18), 8381–8397. https://doi.org/10.1021/acs.jmedchem.6b00748
Wang, M., Carrell, E. J., Ali, Z., Avula, B., Avonto, C., Parcher, J. F., & Khan, I. A. (2014). Comparison of three chromatographic techniques for the detection of mitragynine and other indole and oxindole alkaloids in Mitragyna speciosa (kratom) plants. Journal of Separation Science, 37(12), 1411–1418. https://doi.org/10.1002/jssc.201301389
