A STUDI IN SILICO: POTENSI SENYAWA KATEKIN DAN TURUNANNYA DARI TEH HIJAU SEBAGAI INHIBITOR HGF SERTA PROFIL TOKSISITASNYA
Kata Kunci:
Teh hijau, inhibitor, HGF, antitumor
Abstrak
Teh hijau merupakan salah satu tumbuhan dengan kandungan katekin yang tinggi. Katekin merupakan salah satu metabolit sekunder yang memiliki banyak manfaat dan potensi. Salah satunya sebagai antitumor. Penelitian ini bertujuan untuk mendeskripsikan potensi katekin dan turunan sebagai antitumor inhibitor HGF serta profil toksisitasnya melalui analisis in silico. Ligan yang digunakan dalam penelitian ini adalah katekin, galokatekin, epikatekin, dan epigalokatekin. Hasil penelitian menunjukkan bahwa epikatekin memiliki potensi lebih baik (-6,6 kkal/mol) dibandingkan turunan katekin lainnya. Profil toksisitas keempat katekin tersebut menunjukkan bahwa keempatnya tidak hepatotoksik, tidak mutagentik, tidak karsinogenik, dan memiliki nilai LD50 yang aman. Penelitian lebih lanjut seperti in vitro dan in vivo diperlukan untuk menguak potensinya sebagai antitumor inhibitor HGF.
Referensi
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6. Lambert, J. D., & Elias, R. J. (2010). The antioxidant and pro-oxidant activities of green tea polyphenols: a role in cancer prevention. Archives of Biochemistry and Biophysics, 501(1), 65–72.
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8. Kim, A., Chiu, A., Barone, M. K., Avino, D., Wang, F., Coleman, C. I., & Phung, O. J. (2011). Green tea katekins decrease total and low-density lipoprotein cholesterol: a systematic review and meta-analysis. Journal of the American Dietetic Association, 111(11), 1720–1729.
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11. Kharisma, V., Widyananda, M., Nege, A., Naw, S., & Nugraha, A. (2021). Tea katekin as antiviral agent via apoptosis agonist and triple inhibitor mechanism against HIV-1 infection: A bioinformatics approach. Journal of Pharmacy & Pharmacognosy Research, 9, 435–445.
12. Maeda-Yamamoto, M., Ema, K., & Shibuichi, I. (2007). In vitro and in vivo anti-allergic effects of ‘benifuuki’green tea containing O-methylated katekin and ginger extract enhancement. Cytotechnology, 55, 135–142.
13. Coșarcă, S., Tanase, C., & Muntean, D. L. (2019). Therapeutic aspects of katekin and its derivatives–an update. Acta Biologica Marisiensis, 2(1), 21–29.
14. Ma, Y., Ding, S., Fei, Y., Liu, G., Jang, H., & Fang, J. (2019). Antimicrobial activity of anthocyanins and katekins against foodborne pathogens Escherichia coli and Salmonella. Food Control, 106, 106712.
15. Mechchate, H., Es-Safi, I., Haddad, H., Bekkari, H., Grafov, A., & Bousta, D. (2021). Combination of Katekin, Epikatekin, and Rutin: Optimization of a novel complete antidiabetic formulation using a mixture design approach. The Journal of Nutritional Biochemistry, 88, 108520.
16. Boromand, N., Hasanzadeh, M., ShahidSales, S., Farazestanian, M., Gharib, M., Fiuji, H., Behboodi, N., Ghobadi, N., Hassanian, S. M., & Ferns, G. A. (2018). Clinical and prognostic value of the C‐Met/HGF signaling pathway in cervical cancer. Journal of Cellular Physiology, 233(6), 4490–4496.
17. Lam, B. Q., Dai, L., & Qin, Z. (2016). The role of HGF/c-MET signaling pathway in lymphoma. Journal of Hematology & Oncology, 9(1), 1–8.
18. Stanley, A., Ashrafi, G. H., Seddon, A. M., & Modjtahedi, H. (2017). Synergistic effects of various Her inhibitors in combination with IGF-1R, C-MET and Src targeting agents in breast cancer cell lines. Scientific Reports, 7(1), 3964.
19. Mo, H.-N., & Liu, P. (2017). Targeting MET in cancer therapy. Chronic Diseases and Translational Medicine, 3(03), 148–153.
20. Demkova, L., & Kucerova, L. (2018). Role of the HGF/c-MET tyrosine kinase inhibitors in metastasic melanoma. Molecular Cancer, 17, 1–14.
21. Sururi, A. M., Raihan, M., Aisa, E. R., Safitri, F. N., & Constaty, I. C. (2022). Anti-Inflammatory Activity of Stem Bark Dichloromethane Fraction Syzygium samarangense Extract as COX-2 Inhibitor: A Bioinformatics Approach. Jurnal Kimia Riset, 7(2), 94–100. https://doi.org/10.20473/jkr.v7i2.39662
22. Sururi, A. M., Maharani, D. K., & Wati, F. A. (2023). POTENSI SENYAWA EUGENOL DARI CENGKEH (Syzygium aromaticum) SEBAGAI INHIBITOR PROTEASE HIV-1 (PR). Unesa Journal of Chemistry, Vol 12 No 1 (2023), 26–30. https://ejournal.unesa.ac.id/index.php/unesa-journal-of-chemistry/article/view/52025/42268
23. Trott, O., & Olson, A. J. (2010). AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. Journal of Computational Chemistry, 31(2), 455–461. https://doi.org/10.1002/jcc.21334
24. Banerjee, P., Eckert, A. O., Schrey, A. K., & Preissner, R. (2018). ProTox-II: a webserver for the prediction of toxicity of chemicals. Nucleic Acids Research, 46(W1), W257–W263.
25. Konstorum, A., & Lowengrub, J. S. (2018). Activation of the HGF/c-Met axis in the tumor microenvironment: A multispecies model. Journal of Theoretical Biology, 439, 86–99.
26. Zhang, H., Feng, Q., Chen, W.-D., & Wang, Y.-D. (2018). HGF/c-MET: A Promising Therapeutic Target in the Digestive System Cancers. International Journal of Molecular Sciences, 19(11). https://doi.org/10.3390/ijms19113295
27. Głowacki, E. D., Irimia-Vladu, M., Bauer, S., & Sariciftci, N. S. (2013). Hydrogen-bonds in molecular solids – from biological systems to organic electronics. Journal of Materials Chemistry B, 1(31), 3742–3753. https://doi.org/10.1039/C3TB20193G
28. Cheng, X., Shkel, I. A., O’Connor, K., & Record, M. T. (2020). Experimentally determined strengths of favorable and unfavorable interactions of amide atoms involved in protein self-assembly in water. Proceedings of the National Academy of Sciences, 117(44), 27339 LP – 27345. https://doi.org/10.1073/pnas.2012481117
29. Njoroge, F. G., Chen, K. X., Shih, N.-Y., & Piwinski, J. J. (2008). Challenges in Modern Drug Discovery: A Case Study of Boceprevir, an HCV Protease Inhibitor for the Treatment of Hepatitis C Virus Infection. Accounts of Chemical Research, 41(1), 50–59. https://doi.org/10.1021/ar700109k
30. Shifeng, P., Boopathi, V., Murugesan, M., Mathiyalagan, R., Ahn, J., Xiaolin, C., Yang, D.-U., Kwak, G.-Y., Kong, B. M., Yang, D.-C., Kang, S. C., & Hao, Z. (2022). Molecular Docking and Dynamics Simulation Studies of Ginsenosides with SARS-CoV-2 Host and Viral Entry Protein Targets. Natural Product Communications, 17(11), 1934578X221134331. https://doi.org/10.1177/1934578X221134331
31. Raies, A. B., & Bajic, V. B. (2016). In silico toxicology: computational methods for the prediction of chemical toxicity. Wiley Interdisciplinary Reviews: Computational Molecular Science, 6(2), 147–172.
32. Chang, C. Y., & Schiano, T. D. (2007). Drug hepatotoxicity. Alimentary Pharmacology & Therapeutics, 25(10), 1135–1151.
33. Jamal, Q., Lohani, M., Siddiqui, M., Haneef, D., Gupta, S., & Wadhwa, D. (2012). Molecular interaction analysis of cigarette smoke carcinogens NNK and NNAL with enzymes involved in DNA repair pathways: An in silico approach. Bioinformation, 8, 795–800. https://doi.org/10.6026/97320630008795
34. Wang, D., Kreutzer, D. A., & Essigmann, J. M. (1998). Mutagenicity and repair of oxidative DNA damage: insights from studies using defined lesions. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, 400(1–2), 99–115.
35. Randhawa, M. A. (2009). Calculation of LD50 values from the method of Miller and Tainter, 1944. J Ayub Med Coll Abbottabad, 21(3), 184–185.
2. Preedy, V. R. (2012). Tea in health and disease prevention. Academic Press.
3. Dou, Q. P. (2019). Tea in health and disease. In Nutrients (Vol. 11, Issue 4, p. 929). MDPI.
4. Graham, H. N. (1992). Green tea composition, consumption, and polyphenol chemistry. Preventive Medicine, 21(3), 334–350.
5. Wein, S., Beyer, B., Gohlke, A., Blank, R., Metges, C. C., & Wolffram, S. (2016). Systemic Absorption of Katekins after Intraruminal or Intraduodenal Application of a Green Tea Extract in Cows. PLOS ONE, 11(7), e0159428. https://doi.org/10.1371/journal.pone.0159428
6. Lambert, J. D., & Elias, R. J. (2010). The antioxidant and pro-oxidant activities of green tea polyphenols: a role in cancer prevention. Archives of Biochemistry and Biophysics, 501(1), 65–72.
7. Tipoe, G. L., Leung, T.-M., Hung, M.-W., & Fung, M.-L. (2007). Green tea polyphenols as an anti-oxidant and anti-inflammatory agent for cardiovascular protection. Cardiovascular & Haematological Disorders-Drug Targets (Formerly Current Drug Targets-Cardiovascular & Hematological Disorders), 7(2), 135–144.
8. Kim, A., Chiu, A., Barone, M. K., Avino, D., Wang, F., Coleman, C. I., & Phung, O. J. (2011). Green tea katekins decrease total and low-density lipoprotein cholesterol: a systematic review and meta-analysis. Journal of the American Dietetic Association, 111(11), 1720–1729.
9. EFSA Panel on Dietetic Products, N. and A. (NDA). (2010). Scientific Opinion on the substantiation of health claims related to various food (s)/food constituent (s) and protection of cells from premature aging, antioxidant activity, antioxidant content and antioxidant properties, and protection of DNA, proteins and lipids from oxidative damage pursuant to Article 13 (1) of Regulation (EC) No 1924/2006. EFSA Journal, 8(2), 1489.
10. Kumudavally, K. V, Phanindrakumar, H. S., Tabassum, A., Radhakrishna, K., & Bawa, A. S. (2008). Green tea–A potential preservative for extending the shelf life of fresh mutton at ambient temperature (25±2 C). Food Chemistry, 107(1), 426–433.
11. Kharisma, V., Widyananda, M., Nege, A., Naw, S., & Nugraha, A. (2021). Tea katekin as antiviral agent via apoptosis agonist and triple inhibitor mechanism against HIV-1 infection: A bioinformatics approach. Journal of Pharmacy & Pharmacognosy Research, 9, 435–445.
12. Maeda-Yamamoto, M., Ema, K., & Shibuichi, I. (2007). In vitro and in vivo anti-allergic effects of ‘benifuuki’green tea containing O-methylated katekin and ginger extract enhancement. Cytotechnology, 55, 135–142.
13. Coșarcă, S., Tanase, C., & Muntean, D. L. (2019). Therapeutic aspects of katekin and its derivatives–an update. Acta Biologica Marisiensis, 2(1), 21–29.
14. Ma, Y., Ding, S., Fei, Y., Liu, G., Jang, H., & Fang, J. (2019). Antimicrobial activity of anthocyanins and katekins against foodborne pathogens Escherichia coli and Salmonella. Food Control, 106, 106712.
15. Mechchate, H., Es-Safi, I., Haddad, H., Bekkari, H., Grafov, A., & Bousta, D. (2021). Combination of Katekin, Epikatekin, and Rutin: Optimization of a novel complete antidiabetic formulation using a mixture design approach. The Journal of Nutritional Biochemistry, 88, 108520.
16. Boromand, N., Hasanzadeh, M., ShahidSales, S., Farazestanian, M., Gharib, M., Fiuji, H., Behboodi, N., Ghobadi, N., Hassanian, S. M., & Ferns, G. A. (2018). Clinical and prognostic value of the C‐Met/HGF signaling pathway in cervical cancer. Journal of Cellular Physiology, 233(6), 4490–4496.
17. Lam, B. Q., Dai, L., & Qin, Z. (2016). The role of HGF/c-MET signaling pathway in lymphoma. Journal of Hematology & Oncology, 9(1), 1–8.
18. Stanley, A., Ashrafi, G. H., Seddon, A. M., & Modjtahedi, H. (2017). Synergistic effects of various Her inhibitors in combination with IGF-1R, C-MET and Src targeting agents in breast cancer cell lines. Scientific Reports, 7(1), 3964.
19. Mo, H.-N., & Liu, P. (2017). Targeting MET in cancer therapy. Chronic Diseases and Translational Medicine, 3(03), 148–153.
20. Demkova, L., & Kucerova, L. (2018). Role of the HGF/c-MET tyrosine kinase inhibitors in metastasic melanoma. Molecular Cancer, 17, 1–14.
21. Sururi, A. M., Raihan, M., Aisa, E. R., Safitri, F. N., & Constaty, I. C. (2022). Anti-Inflammatory Activity of Stem Bark Dichloromethane Fraction Syzygium samarangense Extract as COX-2 Inhibitor: A Bioinformatics Approach. Jurnal Kimia Riset, 7(2), 94–100. https://doi.org/10.20473/jkr.v7i2.39662
22. Sururi, A. M., Maharani, D. K., & Wati, F. A. (2023). POTENSI SENYAWA EUGENOL DARI CENGKEH (Syzygium aromaticum) SEBAGAI INHIBITOR PROTEASE HIV-1 (PR). Unesa Journal of Chemistry, Vol 12 No 1 (2023), 26–30. https://ejournal.unesa.ac.id/index.php/unesa-journal-of-chemistry/article/view/52025/42268
23. Trott, O., & Olson, A. J. (2010). AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. Journal of Computational Chemistry, 31(2), 455–461. https://doi.org/10.1002/jcc.21334
24. Banerjee, P., Eckert, A. O., Schrey, A. K., & Preissner, R. (2018). ProTox-II: a webserver for the prediction of toxicity of chemicals. Nucleic Acids Research, 46(W1), W257–W263.
25. Konstorum, A., & Lowengrub, J. S. (2018). Activation of the HGF/c-Met axis in the tumor microenvironment: A multispecies model. Journal of Theoretical Biology, 439, 86–99.
26. Zhang, H., Feng, Q., Chen, W.-D., & Wang, Y.-D. (2018). HGF/c-MET: A Promising Therapeutic Target in the Digestive System Cancers. International Journal of Molecular Sciences, 19(11). https://doi.org/10.3390/ijms19113295
27. Głowacki, E. D., Irimia-Vladu, M., Bauer, S., & Sariciftci, N. S. (2013). Hydrogen-bonds in molecular solids – from biological systems to organic electronics. Journal of Materials Chemistry B, 1(31), 3742–3753. https://doi.org/10.1039/C3TB20193G
28. Cheng, X., Shkel, I. A., O’Connor, K., & Record, M. T. (2020). Experimentally determined strengths of favorable and unfavorable interactions of amide atoms involved in protein self-assembly in water. Proceedings of the National Academy of Sciences, 117(44), 27339 LP – 27345. https://doi.org/10.1073/pnas.2012481117
29. Njoroge, F. G., Chen, K. X., Shih, N.-Y., & Piwinski, J. J. (2008). Challenges in Modern Drug Discovery: A Case Study of Boceprevir, an HCV Protease Inhibitor for the Treatment of Hepatitis C Virus Infection. Accounts of Chemical Research, 41(1), 50–59. https://doi.org/10.1021/ar700109k
30. Shifeng, P., Boopathi, V., Murugesan, M., Mathiyalagan, R., Ahn, J., Xiaolin, C., Yang, D.-U., Kwak, G.-Y., Kong, B. M., Yang, D.-C., Kang, S. C., & Hao, Z. (2022). Molecular Docking and Dynamics Simulation Studies of Ginsenosides with SARS-CoV-2 Host and Viral Entry Protein Targets. Natural Product Communications, 17(11), 1934578X221134331. https://doi.org/10.1177/1934578X221134331
31. Raies, A. B., & Bajic, V. B. (2016). In silico toxicology: computational methods for the prediction of chemical toxicity. Wiley Interdisciplinary Reviews: Computational Molecular Science, 6(2), 147–172.
32. Chang, C. Y., & Schiano, T. D. (2007). Drug hepatotoxicity. Alimentary Pharmacology & Therapeutics, 25(10), 1135–1151.
33. Jamal, Q., Lohani, M., Siddiqui, M., Haneef, D., Gupta, S., & Wadhwa, D. (2012). Molecular interaction analysis of cigarette smoke carcinogens NNK and NNAL with enzymes involved in DNA repair pathways: An in silico approach. Bioinformation, 8, 795–800. https://doi.org/10.6026/97320630008795
34. Wang, D., Kreutzer, D. A., & Essigmann, J. M. (1998). Mutagenicity and repair of oxidative DNA damage: insights from studies using defined lesions. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, 400(1–2), 99–115.
35. Randhawa, M. A. (2009). Calculation of LD50 values from the method of Miller and Tainter, 1944. J Ayub Med Coll Abbottabad, 21(3), 184–185.
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