Studi In Silico Potensi Antikanker Leukemia Limfositik Senyawa Alkaloid Indol terhadap Protein BCL-2
Study of In Silico Anticancer Action Potentials of Lymphocytic Leukemia Indole Alkaloid Compounds Against on BCL-2 Protein
DOI:
https://doi.org/10.25026/jsk.v5i5.1880Abstract
BCL-2 is an anti-apoptotic protein that can inhibit cell death, prolong cell survival time, and turn cells into malignant ones, which is one of the pathways targeted in the development of leukemia therapy by binding and inactivating the BH3 domain pro-apoptotic protein. Indole alkaloids have pharmacological activities and contribute to the development of new drug leads. This study aims to analyze the potential of insilico alkaloids against Bcl-2 in silico. The docking process initiated from preparing the ligand taken from the Pubchem website. The three-dimensional macromolecular structure of the protein used was BCL-2 retrieved from the RCSB Protein Data Bank (www.rcsb.org) with PDB ID number 6O0K. The validation and docking process was carried out using the AutodockTools software program from MGLTools 1.5.6. Chemical bond interaction analysis was carried out using BIOVIA Discovery Studio 2021 Client. The binding energy results from validating the native ligand venetoclax as existing drug is -14.46 kcal/mol. The results obtained from the three ligands, namely aspidodasycarpine, tetrahydroalstonine, and kopsamine have binding energies of -6.76, -7.92, -7.57 kcal/mol respectively. When compared with tetrahydroalstonine which has the smallest value among the three other ligands, it can be concluded that venetoclax is still smaller so that it becomes more potent than tetrahydroalstonine.
Keywords: Indole alkaloids, Cancer, Bcl-2, Docking
Abstrak
BCL-2 adalah protein anti-apoptosis yang dapat menghambat kematian sel, memperpanjang waktu hidup sel, dan mengubah sel menjadi ganas, yang merupakan salah satu jalur yang ditargetkan dalam perkembangan terapi penyakit leukemia dengan mengikat serta menonaktifkan protein pro-apoptosis domain BH3. Alkaloid indol memiliki aktivitas farmakologi dan berkontribusi untuk pengembangan lead obat baru, dimana salah satu senyawa yang paling aktif memiliki berbagai aktivitas farmakologi, yaitu antikanker. Penelitian ini bertujuan untuk menganalisis potensi alkaloid indol terhadap Bcl-2 in silico. Proses docking dimulai dari penyiapan ligan yang diambil dari situs web Pubchem. Struktur makromolekul tiga dimensi protein yang digunakan dalam studi docking ini adalah BCL-2 yang diunduh dari RCSB Protein Data Bank (www.rcsb.org) dengan nomor ID PDB 6O0K. Proses validasi dan docking dilakukan menggunakan perangkat lunak program AutodockTools dari MGLTools 1.5.6. Analisis interaksi ikatan kimia dilakukan menggunakan BIOVIA Discovery Studio 2021 Client. Hasil energi ikatan dari validasi ligan bawaan venetoclax sebagai obat yang telah dikembangkan yaitu -14.46 kkal/mol. Diperoleh hasil dari analisis data energi ikatan dari tiga ligan, yaitu aspidodasycarpine, tetrahydroalstonine, dan kopsamine berurutan sebesar -6,76, -7,92, -7,57 kkal/mol. Apabila dibandingkan dengan tetrahydroalstonine yang memiliki nilai paling kecil diantara ketiga ligan lain maka dapat disimpulkan bahwa venetoclax masih lebih kecil sehingga menjadi lebih poten dibandingkan dengan tetrahydroalstonine.
Kata Kunci: Alkaloid indol, Kanker, BCL-2, Docking
References
H. Wang et al., “Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980–2015: a systematic analysis for the Global Burden of Disease Study 2015,” The Lancet, vol. 388, no. 10053, pp. 1459–1544, Oct. 2016, doi: 10.1016/S0140-6736(16)31012-1.
A. V. Hoffbrand, Kapita Selekta Hematologi. Edisi ke-4, 4th ed. Jakarta: EGC, 2005.
F. Bray, J. Ferlay, I. Soerjomataram, R. L. Siegel, L. A. Torre, and A. Jemal, “Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries,” CA Cancer J Clin, vol. 68, no. 6, pp. 394–424, Nov. 2018, doi: 10.3322/caac.21492.
H. Nagai and Y. H. Kim, “Cancer prevention from the perspective of global cancer burden patterns.,” J Thorac Dis, vol. 9, no. 3, pp. 448–451, Mar. 2017, doi: 10.21037/jtd.2017.02.75.
M. H. Kang and C. P. Reynolds, “Bcl-2 inhibitors: targeting mitochondrial apoptotic pathways in cancer therapy.,” Clin Cancer Res, vol. 15, no. 4, pp. 1126–32, Feb. 2009, doi: 10.1158/1078-0432.CCR-08-0144.
X. Lv et al., “Computational study on novel natural inhibitors targeting BCL2.,” Med Oncol, vol. 38, no. 8, p. 94, Jul. 2021, doi: 10.1007/s12032-021-01513-x.
S. Qian, Z. Wei, W. Yang, J. Huang, Y. Yang, and J. Wang, “The role of BCL-2 family proteins in regulating apoptosis and cancer therapy.,” Front Oncol, vol. 12, p. 985363, 2022, doi: 10.3389/fonc.2022.985363.
Q. Liu and H.-G. Wang, “Anti-cancer drug discovery and development: Bcl-2 family small molecule inhibitors.,” Commun Integr Biol, vol. 5, no. 6, pp. 557–65, Nov. 2012, doi: 10.4161/cib.21554.
S. Ekins, J. Mestres, and B. Testa, “In silico pharmacology for drug discovery: methods for virtual ligand screening and profiling.,” Br J Pharmacol, vol. 152, no. 1, pp. 9–20, Sep. 2007, doi: 10.1038/sj.bjp.0707305.
T. A. Rahman and K. Awang, “In vitro Cytotoxic Effect of Indole Alkaloids from the Roots of Kopsia singapurensis Ridl. against the Human Promyelocytic Leukemia (HL-60) and the Human Cervical Cancer (HeLa) Cel Siow-Ping Tan,” 2015. [Online]. Available: www.globalresearchonline.net
U. Amna, R. Artikel, and K. Kunci, “Isolasi Senyawa Alkaloid Indol dari Ekstrak Akar Kopsia singapurensis Ridl. (Apocynaceae),” 2356, [Online]. Available: www.teknik.unsam.ac.id
C. Kirubhanand et al., “Molecular docking analysis of Bcl-2 with phyto-compounds.,” Bioinformation, vol. 16, no. 6, pp. 468–473, 2020, doi: 10.6026/97320630016468.
D. Dwirosalia et al., “Studi In Silico Potensi Anti Kanker Senyawa Turunan Kumarin Terhadap Protein BCL-2,” Original Article MFF, vol. 25, no. 2, pp. 84–87, 2021, doi: 10.20956/mff.v25i2.13648.
R. Prasetiawati, B. Permana, D. Soni, and S. N. Agung, “Jurnal Ilmiah Farmako Bahari Molecular Docking Study of Xanthone Derivative Compounds of Mangosteen Rind (Garcinia mangostana L.) to ER-? (Estrogen Receptor Alfa) and ER-? (Estrogen Receptor Beta) as Anti-Breast Cancer”, [Online]. Available: http://www.rscb.org/pdb/,
A. Tiara Perdana et al., “Molecular Docking Senyawa Potensial Anticovid-19 Secara In Silico,” 2021. [Online]. Available: http://www.rcsb.org/pdb
Morris, Goodsell, Pique, Lindstrom, and Huey, User Guide AutoDock Version 4.2. Updated for Version 4.2.6. USA: The Scripps Research Institute, 2014.
T. Nauli, “Penentuan Sisi Aktif Selulase Aspergillus Niger dengan Docking Ligan,” Jurnal Kimia Terapan Indonesia, vol. 16, no. 2, 2014.
I. Irwan, “Simulasi Docking Senyawa Napthoquinones Umbi Bawang Tiwai (Eleutherine americana Merr.) terhadap Bakteri Mycobacterium tuberculosis,” Proceeding of Mulawarman Pharmaceuticals Conferences, pp. 2614–4778, 2021, doi: 10.25026/mpc.v13i1.449.
T. M. Syarza, A. Arumsari, and T. M. Fakih, “Studi Interaksi Senyawa Kompleks Besi terhadap Reseptor Hasap pada Pseudomonas aeruginosa Secara In-Silico”, doi: 10.29313/.v6i2.22606.
M. Lasica and M. A. Anderson, “Review of Venetoclax in CLL, AML and Multiple Myeloma.,” J Pers Med, vol. 11, no. 6, May 2021, doi: 10.3390/jpm11060463.
F. Tzifi, C. Economopoulou, D. Gourgiotis, A. Ardavanis, S. Papageorgiou, and A. Scorilas, “The Role of BCL2 Family of Apoptosis Regulator Proteins in Acute and Chronic Leukemias.,” Adv Hematol, vol. 2012, p. 524308, 2012, doi: 10.1155/2012/524308.
F. K. Aziz, C. Nukitasari, F. A. Oktavianingrum, L. W. Aryati, and B. Santoso, “Hasil In Silico Senyawa Z12501572, Z00321025, SCB5631028 dan SCB13970547 dibandingkan Turunan Zerumbon terhadap Human Liver Glycogen Phosphorylase (1l5Q) sebagai Antidiabetes,” Jurnal Kimia VALENSI, vol. 0, no. 0, Dec. 2016, doi: 10.15408/jkv.v0i0.4170.
S. R. Rena, Nurhidayah, and Rustan, “Analisis Molekular Docking Senyawa Garcinia mangostana L. Sebagai Kandidat Anti SARS-CoV-2,” Jurnal Fisika Unand, vol. 11, no. 1, pp. 82–88, 2022.
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