Kuersetin, Penghambat Uridin 5-Monofosfat Sintase Sebagai Kandidat Anti-kanker

Ruswanto Ruswanto, Imam Mustaqim Garna, Lilis Tuslinah, Richa Mardianingrum, Tresna Lestari, Tita Nofianti

Abstract

Kanker adalah pembentukan jaringan baru yang abnormal dan bersifat ganas. Efek toksisitas yang ditimbulkan pada setiap senyawa obat antikanker selalu menjadi problem dalam pengobatan kanker dengan cara kemoterapi, maka dari itu perlu dicari alternatife lain untuk mengatasi kanker. Kuersetin telah diketahui mempunyai aktivitas sitotoksik pada sel kanker tapi belum diketahui mekanisme kerjanya. Pada penelitian ini telah dilakukan penelitiaan in silico untuk mengetahui target reseptor dari senyawa kuersetin melalui identifikasi target reseptor melalui http://lilab.ecust.edu.cn/pharmmapper/ dan studi interaksi melalui metode docking. Hasil menunjukkan bahwa kuersetin memiliki aktivitas pada target reseptor proto-onkogen protein-tirosin kinase dan uridin 5-monofosfat sintase. Berdasarkan nilai energi bebas (∆G) dari hasil docking dapat disimpulkan kuersetin memiliki aktivitas terbaik pada protein target uridin 5-monofosfat sintase dengan nilai energi binding affinity sebesar -8,28617 kkal/mol dan berinteraksi dengan residu asam amino yang sesuai dengan active site dari protein target reseptor uridin 5-monofosfat sintase yaitu membentuk 2 ikatan hidrogen dengan residu Tyr 432 dan Gly 450 dan kontak bagian hidrofobik dengan residu Asn 312, Met 371, pro 417.

Quersetine: Uridine 5-Monophosphate Synthase Inhibitor as Anticancer Candidate. Cancer is the abnormal formation of new tissue and malignant. Toxicity effects inflicted on any anti-cancer drug compounds has always been a problem in the treatment of cancer by chemotherapy, therefore it is necessary to find other alternatives to treat cancer. Quercetin has been known to have cytotoxic activity on cancer cells but unknown mechanism of action. This study has been conducted in silico to determine the receptor target of the quercetin compound through the identification of target receptors by http://lilab.ecust.edu.cn/pharmmapper/ and interaction studies through docking methods. The results showed that the quercetin has activity on the receptor target proto-oncogene protein-tyrosine kinase and uridine 5- monophosphate synthase. Based on free energy value (ΔG) of the docking results we can conclude the quercetin has the best activity of the receptor target uridine 5- monophosphate synthase with a binding affinity energy value of -8.28617 kcal/mol and interacts with the amino acid residues to the active site of the receptor target 5-uridine monophosphate synthase which form two hydrogen bonds with Tyr 432 and Gly 450 and the hydrophobic contact with Asn 312, Met 371, and pro 417.

Keywords

anti-kanker; docking; Kkersetin; pharmmapper.

Full Text:

PDF

References

Adawiyah, R., and Artika, I.M., 2016. Histone Acetyltranferase P300/CBP-Associated Factor Inhibition by Quercetin as Anticancer Drug Candidate with In Silico and In Vitro Approach. International Journal of Pharmacy and Pharmaceutical Sciences 8(5), 1–5.

Adelin, T., Frengki, and Dwinna, A., 2013. Penambatan Molekuler Kurkumin dan Analognya Pada Enzim Siklooksigenase-2. Jurnal Medika Veterinaria 7(1), 0853-1943.

Agistia, Purnomo, H., Tegar, M., and Nugroho A.E., 2013, Interaksi Senyawa Aktif dari Aegle marmelos Correa, sebagai Anti Inflamasi dengan Reseptor COX-1 dan COX-2. Traditional Medicine Journal 18(2).

Baghel, S.S., Shrivastava, N., and Baghel, R.S., 2012, A Review of Quercetin : Antioxidant and Anticancer Properties. World Journal of Pharmacy and Pharmaceutical Sciences 1(1), 146-160.

Chimiche, S., Borsari, V.L., Applicata, B., Luciano, P., Applicata, B., Luciano, P., and Sacchetti, G., 2017. Research Progress in the Modification of Quersetin Leading to Anticancer Agents. Molecules 22(8), 1-27.

Drie, Van, 2007. Monty Kier and the Origin of the Pharmacophore Concept" (PDF), Internet Electronic Journal of Molecular Design 6, 271–279.

Gunasekaran, Ramakrishnan and Balaram, 1996. Disallowed Ramachandran Conformations of Amino Acid Residues in Protein Structures. Journal of Molecular Biology 264, 191 – 198.

http://www,depkes,go,id/, Data Kanker, [Diakses pada tanggal 27 Februari 2016, jam 14,15 WIB].

Hashemzaei, M., Far, A.D., Yari, A., Heravi, R.E., Tabrizian, K., Taghdisi, S.M., and Kouretas, D., 2017. Anticancer and Apoptosis Inducing Effects of Quercetin In Vitro and In Vivo. Oncology Reports 38, 819–828.

Ikawati, M., Andy, E.W., Navista, S.O., and Rosa, A., 2008. Pemanfaatan Benalu sebagai Antikanker. Fakultas Farmasi Universitas Gadjah Mada. Yogyakarta.

Katzung and Bertram G., 2010. Farmakologi Dasar & Klinik/Alih Bahasa, Aryandhito Widhoi Nugroho, Leo Rendy, Linda Dwijayanthi; editor bahasa Indonesia, Windriya Kerta Nirmala [et al.,],-Ed, 10, Jakarta :EGC, pp. 927.

Liu, X., Ouyang, S., Yu, B., Huang, K., and Liu, Y., 2010. PharmMapper Server: a Web Server for Potential Drug Target Identification Via Pharmacophore Mapping Approach, Nucleic Acids Research 38

Pebriana, R.B., Romadhon, and Yunanto, 2008. Docking Kurkumin dan Senyawa Analognya pada Reseptor Progesteron: Studi Interaksinya sebagai Selective Progesterone Receptor Modulator (SPRMSs). PHARMACON 9(1), 14–20.

Priya, E.S., Selvakumar, K., Bavithra, S., Elumalai, P., Arunkumar, R., Singh, P.R., and Arunakaran, J., 2013. Anti-cancer Activity of Quercetin in Neuroblastoma : an in vitro Approach. Neurological Sciences 35, 163.

Purnomo, 2013. Kimia Komputasi: Molekular Docking Plants [Protein-Ligan-Ant-System]. Yogyakarta: Pustaka Pelajar.

Ruswanto, 2015. Molecular Docking Empat Turunan Isonicotinohydrazide pada Myobacterium Tuberculosis Enoyl-Acyl Carrier Protein Reductase (InhA). Jurnal Kesehatan Bakti Tunas Husada 13(1).

Ruswanto, Mardhiaha, Mardianingrum, R., and Novitriani, K., 2015. Sintesis dan Studi In Silico Senyawa 3-Nitro-N'-[(Pyridin-4-Yl) Carbonyl] Benzohydrazide sebagai Kandidat Antituberkulosis, Chimica et Natura Acta 3(2), 54-61.

Wallace, A.C., Laskowski, R.A., and Thornton, J.M., 1996. LIGPLOT: a Program to Generate Schematic Diagrams of Protein-Ligand Interactions. Protein engineering 8, 127-134.

Article Metrics

Abstract view : 173 times
PDF - 0 times

Refbacks

  • There are currently no refbacks.