Analisa in Silico Kunyit (Curcuma longa) sebagai Inhibitor Murine Double Minute 2 Protein untuk Terapi Glioblastoma Multiforme
DOI:
https://doi.org/10.30649/obj.v3i2.61Kata Kunci:
Glioblastoma multiforme, Curcuma longa, MDM 2, Autodock 4.2Abstrak
Tumor otak meliputi berbagai kanker yang tumbuh dari sel otak (tumor otak primer)
ataupun berasal dari tumor sistemik yang mengalami metastasis ke otak (tumor otak
sekunder). Dari seluruh tipe tumor otak primer, Glioblastoma Multiforme merupakan
tumor otak yang paling sering dijumpai dan merupakan salah satu yang paling ganas.
Pada 85% kasus Glioblastoma Multiforme, umumnya ditemukan kaitan dengan adanya
gangguan tingkat molekuler pada jalur tumor suppresor gene p53, sehingga semakin
banyak terapi yang dikembangkan dengan berfokus pada jalur ini. Salah satu jalur yang
dapat dipakai sebagai model terapi adalah menginhibisi protein murine double minute 2
yang merupakan inhibitor dari p53. Kunyit (curcuma longa) adalah salah satu tanamantradisional yang sudah sangat sering digunakan dalam dunia medis dan berbagai ekstrak
nya telah diteliti mempunyai efek anti-kanker.
Penelitian ini adalah sebuah studi in silico yang meneliti potensi berbagai bahan
kimia aktif dari kunyit sebagai inhibitor pada protein murine double minute 2
menggunakan AutoDock 4.2 dan berdasarkan prinsip algoritma genetik Lamarckian.
Hasil docking menunjukkan binding energy berkisar dari rentang -4.81 kcal/mol sampai -
2.34 kcal/mol, dengan senyawa curcumenol mempunyai binding energy yang paling kecil
dan curcumin mempunyai binding energy yang paling besar. Studi ini dapat digunakan
sebagai dasar untuk melakukan penelitian lebih lanjut (in vivo dan in vitro) terkait bahan
kimia aktif kunyit dan efek nya sebagai terapi Glioblastoma Multiforme..
Referensi
Adejoro, I., Waheed, S. and Adeboye, O. (2016). Molecular Docking Studies of
Lonchocarpus cyanescens Triterpenoids as Inhibitors for Malaria. Journal of Physical
Chemistry & Biophysics, 6(2).
Afriza, D., Suriyah, W. and Ichwan, S. (2018). In silicoanalysis of molecular
interactions between the anti-apoptotic protein survivin and dentatin, nordentatin, and
quercetin. Journal of Physics: Conference Series, 1073, p.032001.
Brust, J., 2012. Current Diagnosis & Treatment Neurology. 2nd ed.
Butowski, N. (2015). Epidemiology and Diagnosis of Brain Tumors. CONTINUUM:
Lifelong Learning in Neurology, 21, pp.301-313.
Daina, A., Michielin, O. and Zoete, V. (2017). SwissADME: a free web tool to
evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small
molecules. Scientific Reports, 7(1).
Dundas, J., Ouyang, Z., Tseng, J., Binkowski, A., Turpaz, Y. and Liang, J. (2006).
CASTp: computed atlas of surface topography of proteins with structural and
topographical mapping of functionally annotated residues. Nucleic Acids Research,
(Web Server), pp.W116-W118.
Forte, I., Indovina, P., Iannuzzi, C., Cirillo, D., Di Marzo, D., Barone, D., Capone,
F., Pentimalli, F. and Giordano, A. (2019). Targeted therapy based on p53 reactivation
reduces both glioblastoma cell growth and resistance to temozolomide. International
Journal of Oncology.
Guo, L., Cai, X., Lee, J., Kang, S., Shin, E., Zhou, H., Jung, J. and Kim, Y. (2008).
Comparison of suppressive effects of demethoxycurcumin and bisdemethoxycurcumin
on expressions of inflammatory mediators In Vitro and In Vivo. Archives of Pharmacal
Research, 31(4), pp.490-496.
Hari, S. (2019). In silico molecular docking and ADME/T analysis of plant
compounds against IL17A and IL18 targets in gouty arthritis. Journal of Applied
Pharmaceutical Science, 9(7), pp.18-26.
Huang, Y., Rose, P. and Hsu, C. (2015). Citing a Data Repository: A Case Study
of the Protein Data Bank. PLOS ONE, 10(8), p.e0136631.
Hucklenbroich, J., Klein, R., Neumaier, B., Graf, R., Fink, G., Schroeter, M. and
Rueger, M. (2014). Aromatic-turmerone induces neural stem cell proliferation in vitro and
in vivo. Stem Cell Research & Therapy, 5(4), p.100.
Kim, S., Thiessen, P., Bolton, E., Chen, J., Fu, G., Gindulyte, A., Han, L., He, J.,
He, S., Shoemaker, B., Wang, J., Yu, B., Zhang, J. and Bryant, S. (2015). PubChem
Substance and Compound databases. Nucleic Acids Research, 44(D1), pp.D1202-
D1213.
Klinger, N. and Mittal, S. (2016). Therapeutic Potential of Curcumin for the
Treatment of Brain Tumors. Oxidative Medicine and Cellular Longevity, 2016, pp.1-14.
Kocaadam, B. and Şanlier, N. (2015). Curcumin, an active component of turmeric
(Curcuma longa), and its effects on health. Critical Reviews in Food Science and Nutrition,
(13), pp.2889-2895.
Lipinski, C., Lombardo, F., Dominy, B. and Feeney, P. (2001). Experimental and
computational approaches to estimate solubility and permeability in drug discovery and
development settings 1PII of original article: S0169-409X(96)00423-1. The article was
originally published in Advanced Drug Delivery Reviews 23 (1997) 3–25. 1. Advanced
Drug Delivery Reviews, 46(1-3), pp.3-26.
Lo, J., Kamarudin, M., Hamdi, O., Awang, K. and Kadir, H. (2015). Curcumenol
isolated from Curcuma zedoaria suppresses Akt-mediated NF-κB activation and p38
MAPK signaling pathway in LPS-stimulated BV-2 microglial cells. Food & Function, 6(11),
pp.3550-3559.
Morris, G., Goodsell, D., Halliday, R., Huey, R., Hart, W., Belew, R. and Olson, A.
(1998). Automated docking using a Lamarckian genetic algorithm and an empirical
binding free energy function. Journal of Computational Chemistry, 19(14), pp.1639-1662.
Park, S., Jin, M., Kim, Y., Kim, Y. and Lee, S. (2012). Anti-inflammatory effects of
aromatic-turmerone through blocking of NF-κB, JNK, and p38 MAPK signaling pathways
in amyloid β-stimulated microglia. International Immunopharmacology, 14(1), pp.13-20.
Sulfahri, Arif, A., Iskandar, I. and Wardhani, R. (2019). In silico approach of
antidiabetic compounds from Caesalpinia crista seed through docking analysis and
ADMET predictions. Journal of Physics: Conference Series, 1341, p.022001.
Togar, B., Turkez, H., Tatar, A., Hacimuftuoglu, A. and Geyikoglu, F. (2014).
Cytotoxicity and genotoxicity of zingiberene on different neuron cell lines in
vitro. Cytotechnology, 67(6), pp.939-946.
Wang, H., Oo Khor, T., Shu, L., Su, Z., Fuentes, F., Lee, J. and Tony Kong, A.
(2012). Plants vs. Cancer: A Review on Natural Phytochemicals in Preventing and Treating Cancers and Their Druggability. Anti-Cancer Agents in Medicinal Chemistry,
(10), pp.1281-1305.
Zhang, Y., Dube, C., Gibert, M., Cruickshanks, N., Wang, B., Coughlan, M., Yang,
Y., Setiady, I., Deveau, C., Saoud, K., Grello, C., Oxford, M., Yuan, F. and Abounader, R.
(2018). The p53 Pathway in Glioblastoma. Cancers, 10(9), p.297
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