Skrining senyawa Combretum Indicum sebagai inhibitor Caspase 3 secara In Silico

Samsul Hadi, Salma Salma, Amalia khairunnisa, Suci Kamelia

Abstract


Osteoarthritis ialah gangguan sendi degeneratif yang ditandai dengan erosi cartilage artikular. Salah satu protein yang mempunyai peran besar dalam penyakit ini adalah caspase sub type 3. Sehingga tujuan dari penelitian ini adalah skrining senyawa belanda yang berpotensi sebagai inhibitor caspase 3. Metode dari penelitian ini menggunakan seanyawa yang terkandung dalam Combretum indicum, data ini kemudian dilakukan docking menggunakan software PLANTS. Hasil dari penelitian ini adalah scor docking dari masing masing senyawa yaitu Isatin Sulfonamide -90,8975; Casuariin -92,4942; asquisqualic acid -90,8911; 1-desgalloyleugeniin -100,988; arachidonic acid -63,4613; Punicalin -88,2142; linoleic acid - 97,4111; gallic acid -59,1281; Rutin-95,3717; ellagic acid -63,6793; methyl ursolate -77,5611; flavogallonic acid -80,8221; Quisqualic acid -63,1281; brevifolin carboxylic acid -71,5203; Trigonelline-59,8987; Quercetin -74,4091; quinoline-4-carbonitrile -61,5971; β-sitosterol -87,3881; Pedunculagin-86,843 Lupeol -76,4221; Punicalagin -82,1754; linalool -67,8673; Eugeniin -100,7541.Oleh karena itu senyawa yang berpotensi sebagai inhibitor caspase 3 adalah Rutin, linoleic acid, asquisqualic acid, Eugenin, Casuariin, 1-desgalloyleugeniin.

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Keywords


Osteoarthritis; caspase: PLANT

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References


Enari, M., Sakahira, H., Yokoyama, H., Okawa, K., Iwamatsu, A., & Nagata, S. (1998). A caspase-activated DNase that degrades DNA during apoptosis, and its inhibitor ICAD. Nature, 391(6662), 43–50. https://doi.org/10.1038/34112

Espín, R., Roca, F. J., Candel, S., Sepulcre, M. P., González-Rosa, J. M., Alcaraz-Pérez, F., Meseguer, J., Cayuela, M. L., Mercader, N., & Mulero, V. (2013). TNF receptors regulate vascular homeostasis in zebrafish through a caspase-8, caspase-2 and P53 apoptotic program that bypasses caspase-3. Disease Models & Mechanisms, 6(2), 383–396. https://doi.org/10.1242/dmm.010249

Garcia-Calvo, M., Peterson, E. P., Leiting, B., Ruel, R., Nicholson, D. W., & Thornberry, N. A. (1998). Inhibition of human caspases by peptide-based and macromolecular inhibitors. The Journal of Biological Chemistry, 273(49), 32608–32613. https://doi.org/10.1074/jbc.273.49.32608

Hakem, R., Hakem, A., Duncan, G. S., Henderson, J. T., Woo, M., Soengas, M. S., Elia, A., de la Pompa, J. L., Kagi, D., Khoo, W., Potter, J., Yoshida, R., Kaufman, S. A., Lowe, S. W., Penninger, J. M., & Mak, T. W. (1998). Differential requirement for caspase 9 in apoptotic pathways in vivo. Cell, 94(3), 339–352. https://doi.org/10.1016/s0092-8674(00)81477-4

Hatori, M., Klatte, K. J., Teixeira, C. C., & Shapiro, I. M. (1995). End labeling studies of fragmented DNA in the avian growth plate: evidence of apoptosis in terminally differentiated chondrocytes. Journal of Bone and Mineral Research : The Official Journal of the American Society for Bone and Mineral Research, 10(12), 1960–1968. https://doi.org/10.1002/jbmr.5650101216

Huang, G., Lee, X., Bian, Y., Shao, Z., Sheng, G., Pepinsky, R. B., & Mi, S. (2013). Death receptor 6 (DR6) antagonist antibody is neuroprotective in the mouse SOD1G93A model of amyotrophic lateral sclerosis. Cell Death & Disease, 4(10), e841. https://doi.org/10.1038/cddis.2013.378

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

Karaplis, A. C., & Vautour, L. (1997). Parathyroid hormone-related peptide and the parathyroid hormone/parathyroid hormone-related peptide receptor in skeletal development. Current Opinion in Nephrology and Hypertension, 6(4), 308–313. https://doi.org/10.1097/00041552-199707000-00002

Kuhn, M., von Mering, C., Campillos, M., Jensen, L. J., & Bork, P. (2008). STITCH: interaction networks of chemicals and proteins. Nucleic Acids Research, 36(Database issue), D684–D688. https://doi.org/10.1093/nar/gkm795

Lee, D., Long, S. A., Adams, J. L., Chan, G., Vaidya, K. S., Francis, T. A., Kikly, K., Winkler, J. D., Sung, C. M., Debouck, C., Richardson, S., Levy, M. A., DeWolf, W. E. J., Keller, P. M., Tomaszek, T., Head, M. S., Ryan, M. D., Haltiwanger, R. C., Liang, P. H., … Nuttall, M. E. (2000). Potent and selective nonpeptide inhibitors of caspases 3 and 7 inhibit apoptosis and maintain cell functionality. The Journal of Biological Chemistry, 275(21), 16007–16014. https://doi.org/10.1074/jbc.275.21.16007

Lee, H., Shin, E. A., Lee, J. H., Ahn, D., Kim, C. G., Kim, J.-H., & Kim, S.-H. (2018). Caspase inhibitors: a review of recently patented compounds (2013-2015). Expert Opinion on Therapeutic Patents, 28(1), 47–59. https://doi.org/10.1080/13543776.2017.1378426

Mesner, P. W. J., Budihardjo, I. I., & Kaufmann, S. H. (1997). Chemotherapy-induced apoptosis. Advances in Pharmacology (San Diego, Calif.), 41, 461–499. https://doi.org/10.1016/s1054-3589(08)61069-8

Mollazadeh, S., Fazly Bazzaz, B. S., & Kerachian, M. A. (2015). Role of apoptosis in pathogenesis and treatment of bone-related diseases. Journal of Orthopaedic Surgery and Research, 10, 15. https://doi.org/10.1186/s13018-015-0152-5

Nicholson, D. W., & Thornberry, N. A. (1997). Caspases: killer proteases. Trends in Biochemical Sciences, 22(8), 299–306. https://doi.org/10.1016/s0968-0004(97)01085-2

Park, C., Lee, W. S., Go, S.-I., Nagappan, A., Han, M. H., Hong, S. H., Kim, G. S., Kim, G. Y., Kwon, T. K., Ryu, C. H., Shin, S. C., & Choi, Y. H. (2014). Morin, a flavonoid from moraceae, induces apoptosis by induction of BAD protein in human leukemic cells. International Journal of Molecular Sciences, 16(1), 645–659. https://doi.org/10.3390/ijms16010645

Wang, F.-L., Connor, J. R., Dodds, R. A., James, I. E., Kumar, S., Zou, C., Lark, M. W., Gowen, M., & Nuttall, M. E. (2000). Differential expression of Egr-1 in osteoarthritic compared to normal adult human articular cartilage. Osteoarthritis and Cartilage, 8(3), 161–169. https://doi.org/https://doi.org/10.1053/joca.1999.0295

Yedjou, C. G., Milner, J. N., Howard, C. B., & Tchounwou, P. B. (2010). Basic apoptotic mechanisms of lead toxicity in human leukemia (HL-60) cells. International Journal of Environmental Research and Public Health, 7(5), 2008–2017. https://doi.org/10.3390/ijerph7052008

Zhu, X., Zhang, K., Wang, Q., Chen, S., Gou, Y., Cui, Y., & Li, Q. (2015). Cisplatin-mediated c-myc overexpression and cytochrome c (cyt c) release result in the up-regulation of the death receptors DR4 and DR5 and the activation of caspase 3 and caspase 9, likely responsible for the TRAIL-sensitizing effect of cisplatin. Medical Oncology (Northwood, London, England), 32(4), 133. https://doi.org/10.1007/s12032-015-0588-9




DOI: https://doi.org/10.33508/jfst.v9i2.3999