In silico study of columbin from Tinospora crispa L as dihydrofolate reductase-thymidylate synthase (DHFR-TS) inhibitor
Abstract
The Brotowali plant is used to treat malaria. Tinospora crispa L contains active compounds that are good for health and has been widely used for medicine. Crude extract from Tinospora crispa L can be used as target dihydrofolate reductase-thymidylate synthase (DHFR-TS). This research study was to analyse the potential chemical content of Tinospora crispa L in the form of columbine compounds as a focus of malaria therapy through inhibition of dihydrofolate reductase-thymidylate synthase (DHFR-TS). In silico research method, columbine (CID: 188289) ligand was obtained from Pubchem while DHFR-TS (PDB ID 2bl9) protein was obtained from Protein Data Bank, ligands and proteins were interacted using HEX 8.0.0.0 and visualised using discovery studio. The results obtained are six amino acid residues that bind to the DHFR-TS protein. This binding has an impact on the work function of the DHFR-TS protein. Physicochemical analysis shows that the ligand acts as a donor and acceptor so that the protein is formed and the ligand becomes very strong. This interaction is also supported by amino acid residues that act as supports by forming Van der Waals forces outside of the Van hydrogen bonding forces, pi-Alkyl and Pi also provide support in order to increase the strength and stabilisation of the. Based on the discussion, it can be concluded that the columbine content in Tinospora crispa L has potential as a therapy and treatment for malaria through inhibition of DHFR-TS.
Tanaman Brotowali digunakan untuk mengobati penyakit malaria. Tinospora crispa L mengandung senyawa aktif yang baik untuk kesehatan dan telah banyak digunakan untuk pengobatan. Ekstrak kasar dari Tinospora crispa L dapat digunakan sebagai target dihydrofolate reductase-thymidylate synthase (DHFR-TS). Penelitian ini bertujuan untuk menganalisis potensi kandungan kimia Tinospora crispa L berupa senyawa kolumbin sebagai fokus terapi malaria melalui penghambatan dihydrofolate reductase-thymidylate synthase (DHFR-TS). Metode penelitian in silico diperoleh ligan kolumbin (CID: 188289) dari Pubchem sedangkan protein DHFR-TS (PDB ID 2bl9) diperoleh dari Protein Data Bank, ligan dan protein diinteraksikan menggunakan HEX 8.0.0.0 dan divisualisasikan menggunakan discovery studio. Hasil yang diperoleh adalah enam residu asam amino yang berikatan dengan protein DHFR-TS. Pengikatan ini berdampak pada fungsi kerja protein DHFR-TS. Analisis fisikokimia menunjukkan bahwa ligan berperan sebagai donor dan akseptor sehingga protein yang terbentuk dan ligan menjadi sangat kuat. Interaksi ini juga didukung oleh residu asam amino yang bertindak sebagai pendukung dengan membentuk gaya Van der Waals di luar gaya ikatan hidrogen Van, pi-Alkil dan Pi juga memberikan dukungan dalam rangka meningkatkan kekuatan dan stabilisasi. Berdasarkan pembahasan dapat disimpulkan bahwa kandungan kolumbin pada Tinospora crispa L berpotensi sebagai terapi dan pengobatan malaria melalui penghambatan DHFR-TS.
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Ahmad, N., Fazal, H., Abbasi, B. H., Farooq, S., Ali, M., & Khan, M. A. (2012). Biological role of Piper nigrum L. (Black pepper): A review. Asian Pacific Journal of Tropical Biomedicine, 2(3), S1945–S1953. https://doi.org/10.1016/S2221-1691(12)60524-3
Ahmad, N. I., Bunga, Y. N., & Bare, Y. (2019). Etnobotani Tanaman Cabai Merah Keriting (Capsicum Annum L.) Di Desa Waiwuring, Kecamatan Witihama Kabupaten Flores Timur. Spizaetus: Jurnal Biologi dan Pendidikan Biologi, 2(2), 10. http://dx.doi.org/10.55241/spibio.v2i2.46
Aroonsri, A., Akinola, O., Posayapisit, N., Songsungthong, W., Uthaipibull, C., Kamchonwongpaisan, S., … Shaw, P. J. (2016). Identifying antimalarial compounds targeting dihydrofolate reductase-thymidylate synthase (DHFR-TS) by chemogenomic profiling. International Journal for Parasitology, 46(8), 527–535. https://doi.org/10.1016/j.ijpara.2016.04.002
Bare, Y. (2021). ANALISIS SENYAWA FITOSTEROL Cymbopogon citratus dan Curcuma longa SEBAGAI ANTIALZHEIMER. Biopendix: Jurnal Biologi, Pendidikan dan terapan, 7(2), 53–159. https://doi.org/10.30598/biopendixvol7issue2page153-159
Bare, Y., & Sari, D. R. T. (2021). Pengembangan Lembar Kerja Mahasiswa (LKM) Berbasis Inkuiri Pada Materi Interaksi Molekuler. BioEdUIN, 11(1), 8. https://doi.org/10.15575/bioeduin.v11i1.12077
Bare, Y., Helvina, M., Krisnamurti, G. C., & S, M. (2020). The Potential Role of 6-gingerol and 6-shogaol as ACE Inhibitors in Silico Study. Biogenesis: Jurnal Ilmiah Biologi, 8(2), 210. https://doi.org/10.24252/bio.v8i2.15704
Bare, Y., Indahsari, L. I. N., Sari, D. R. T., & Watuguly, T. (2021). In Silico Study: Potential Prediction of Curcuma longa And Cymbopogon citratus Essential Oil As Lipoxygenase Inhibitor Yohanes. JSMARTech, 02(02), 76–80. https://doi.org/10.21776/ub.jsmartech.2021.002.02.75 In
Bare, Y., Maulidi, A., Sari, D. R. T., & Tiring, S. S. N. D. (2019). Studi in Silico Prediksi Potensi 6-Gingerol sebagai inhibitor c-Jun N-terminal kinases (JNK). Jurnal Jejaring Matematika Dan Sains, 1(2), 59–63. https://doi.org/10.36873/jjms.v1i2.211
Cui, L., Mharakurwa, S., Ndiaye, D., Rathod, P. K., & Rosenthal, P. J. (2015). Antimalarial Drug Resistance: Literature Review and Activities and Findings of the ICEMR Network. The American Journal of Tropical Medicine and Hygiene, 93(3_Suppl), 57–68. https://doi.org/10.4269/ajtmh.15-0007
de Mendonça, V. R. R., Goncalves, M. S., & Barral-Netto, M. (2012). The Host Genetic Diversity in Malaria Infection. Journal of Tropical Medicine, 2012, 1–17. https://doi.org/10.1155/2012/940616
Dumeva, A., & Fitriah, S. (2016). PENGARUH EKSTRAK BATANG BROTOWALI (Tinospora crispa) TERHADAP KEMATIAN LARVA NYAMUK Aedes aegypti. Jurnal Biota, 2(2), 7.
Elfi, T. N., Bunga, Y. N., & Bare, Y. (2021). Studi Aktivitas Biologi Secara In Silico Senyawa Nonivamide Dan Nordihydrocapsaicin Sebagai Anti Inflamasi. Florea : Jurnal Biologi dan Pembelajarannya, 8(2), 82. https://doi.org/10.25273/florea.v8i2.9983
Gibson, M. W., Dewar, S., Ong, H. B., Sienkiewicz, N., & Fairlamb, A. H. (2016). Trypanosoma brucei DHFR-TS Revisited: Characterisation of a Bifunctional and Highly Unstable Recombinant Dihydrofolate Reductase-Thymidylate Synthase. PLOS Neglected Tropical Diseases, 10(5), e0004714. https://doi.org/10.1371/journal.pntd.0004714
Gorelova, V., De Lepeleire, J., Van Daele, J., Pluim, D., Meï, C., Cuypers, A., Leroux, O., Rébeillé, F., Schellens, J. H. M., Blancquaert, D., Stove, C. P., & Van Der Straeten, D. (2017). Dihydrofolate Reductase/Thymidylate Synthase Fine-Tunes the Folate Status and Controls Redox Homeostasis in Plants. The Plant Cell, 29(11), 2831–2853. https://doi.org/10.1105/tpc.17.00433
Kongsaeree, P., Khongsuk, P., Leartsakulpanich, U., Chitnumsub, P., Tarnchompoo, B., Walkinshaw, M. D., & Yuthavong, Y. (2005). Crystal structure of dihydrofolate reductase from Plasmodium vivax: Pyrimethamine displacement linked with mutation-induced resistance. Proceedings of the National Academy of Sciences of the United States of America, 102(37), 13046–13051. https://doi.org/10.1073/pnas.0501747102
Krisnamurti, G. C., Thian, B. K., Krisnamurti, G. C., Ratih, D., Sari, T., & Bare, Y. (2021). Capsaicinoids from Capsicum annuum as an Alternative FabH Inhibitor of Mycobacterium Tuberculosis: In Silico Study Capsaicinoids from Capsicum annuum as an Alternative FabH Inhibitor of Mycobacterium Tuberculosis: In Silico Study. Makara Journal of Science, 25(4), 195–202. https://doi.org/10.7454/mss.v25i4.1248
Landau, M. J., Sharma, H., & Anderson, K. S. (2013). Selective peptide inhibitors of bifunctional thymidylate synthase-dihydrofolate reductase from Toxoplasma gondii provide insights into domain-domain communication and allosteric regulation: Peptide Inhibitors of Parasitic TS-DHFR. Protein Science, 22(9), 1161–1173. https://doi.org/10.1002/pro.2300
Luzz, M., Berman, J., Toledo, J., Llinas, N., Gutierrez, P., Soto, J., Dunne, M., & Cedeño, N. (2001). Plasmodium vivax clinically resistant to chloroquine in Colombia. The American Journal of Tropical Medicine and Hygiene, 65(2), 90–93. https://doi.org/10.4269/ajtmh.2001.65.90
Macindoe, G., Mavridis, L., Venkatraman, V., Devignes, M. D., & Ritchie, D. W. (2010). HexServer: An FFT-based protein docking server powered by graphics processors. Nucleic Acids Research, 38(SUPPL. 2), 445–449. https://doi.org/10.1093/nar/gkq311
Pires, D. E. V., Blundell, T. L., & Ascher, D. B. (2015). pkCSM: Predicting small-molecule pharmacokinetic and toxicity properties using graph-based signatures. Journal of Medicinal Chemistry, 58(9), 4066–4072. https://doi.org/10.1021/acs.jmedchem.5b00104
Ritchie, D. W., Kozakov, D., & Vajda, S. (2008). Accelerating and focusing protein-protein docking correlations using multi-dimensional rotational FFT generating functions. Bioinformatics, 24(17), 1865–1873. https://doi.org/10.1093/bioinformatics/btn334
Sari, D. R. T., Safitri, A., Cairns, J. R. K., & Fatchiyah, F. (2020a). Anti-Apoptotic Activity of Anthocyanins has Potential to inhibit Caspase-3 Signaling. Journal of Tropical Life Science, 10(1), 15–25. https://doi.org/10.11594/jtls.10.01.03
Sari, D. R. T., Safitri, A., Cairns, J. R. K., & Fatchiyah, F. (2020b). Virtual screening of black rice anthocyanins as antiobesity through inhibiting TLR4 and JNK pathway Virtual screening of black rice anthocyanins as antiobesity through inhibiting TLR4 and JNK pathway. Journal of Physics: Conference Series PAPER, 1665(1), 1–7. https://doi.org/10.1088/1742-6596/1665/1/012024
Yesi, Zen, S., & Achyani. (2019). Pengaruh Variasi Dosis Ekstrak Batang Brotowali (Trinospora crispa L.) Terhadap Mortalitas Hama Kutu Daun (Aphis gossypii L.) Tanaman Mentimun (Cucumis sativus L.) Sebagai Sumber Belajar Biologi. BIOEDUKASI Jurnal Pendidikan Biologi, 10(2).
DOI: https://doi.org/10.24036/0202261116090-0-00
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