Article Sidebar

Submitted
Oct 18, 2023
Published
Aug 31, 2024
Download
Pdf
Statistic
Read Counter : 251 Download : 184

Downloads

Download data is not yet available.

Main Article Content

Abstract

Colon cancer is a degenerative disease that attacks the large intestine through a process of initiation, promotion and progression. Related research reports that overexpression of the AKT1 protein was found to be 60-70% and p53 at 50%. This research analyses the affinity, stability and interaction of gallic acid derivative compounds and reference ligands with the target proteins AKT1 and p53 by molecular docking. The study stages carried out include preparation and optimisation of target proteins and ligand compounds, file creation and simulation processes, and analysis and visualisation of docking results. The docking simulation results show that four gallic acid derivative compounds provide potential inhibitory activity against the AKT1 and p53 proteins based on binding energy values. BG and 2HBG compounds have strong inhibitory power against target proteins, thus enabling the formation of strong interactions and complexity towards the active site of amino acids with a bond distance of <3.0 Å. Thus, gallic acid derivative compounds have potential as inhibitors and are expected to activate other proteins, causing cancer cell apoptosis.

Keywords

AKT1 and p53 Colon cancer Gallic acid and its derivatives Molecular docking

Article Details

Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

References

  1. Abbasi, M., Sadeghi-Aliabadi, H., Hassanzadeh, F., & Amanlou, M. (2015). Prediction of dual agents as an activator of mutant p53 and inhibitor of Hsp90 by docking, molecular dynamic simulation and virtual screening. Journal of Molecular Graphics and Modelling, 61(7), 186–195. https://doi.org/10.1016/j.jmgm.2015.08.001
  2. Ahmed, M. (2020). Colon Cancer: A Clinician’s Perspective in 2019. Gastroenterology Research, 13(1), 1–10. https://doi.org/10.14740/gr1239
  3. Al-saffar, N. M. S., Troy, H., Fong, A. W. Te, Paravati, R., Jackson, L. E., Gowan, S., Boult, J. K. R., Robinson, S. P., Eccles, S. A., Yap, T. A., Leach, M. O., & Chung, Y. (2018). Metabolic biomarkers of response to the AKT inhibitor MK-2206 in pre-clinical models of human colorectal and prostate carcinoma. British Journal of Cancer, 119(9), 1118–1128. https://doi.org/10.1038/s41416-018-0242-3
  4. AL Zahrani, N. A., El-Shishtawy, R. M., & Asiri, A. M. (2020). Recent developments of gallic acid derivatives and their hybrids in medicinal chemistry: A review. European Journal of Medicinal Chemistry, 204(20), 1–103. https://doi.org/10.1016/j.ejmech.2020.112609
  5. Anantharaju, P. G., Gowda, P. C., Vimalambike, M. G., & Madhunapantula, S. V. (2016). An Overview on the Role of Dietary Phenolics for the Treatment of Cancers. Nutrition Journal, 15(1), 1–16. https://doi.org/10.1186/s12937-016-0217-2
  6. Badhani, B., Sharma, N., & Kakkar, R. (2015). Gallic acid: A versatile antioxidant with promising therapeutic and industrial applications. RSC Advances, 5(35), 27540–27557. https://doi.org/10.1039/c5ra01911g
  7. Bai, J., Zhang, Y., Tang, C., Hou, Y., Ai, X., Chen, X., Zhang, Y., Wang, X., & Meng, X. (2021). Biomedicine & Pharmacotherapy Gallic acid : Pharmacological activities and molecular mechanisms involved in inflammation-related diseases. Biomedicine & Pharmacotherapy, 133(November 2020), 110985.
  8. https://doi.org/10.1016/j.biopha.2020.110985
  9. Bergers, G., & Fendt, S.-M. (2021). The metabolism of cancer cells during metastasis. Nature Reviews Cancer, 21(3), 162–180. https://doi.org/10.1038/s41568-020-00320-2
  10. Boutelle, A. M., & Attardi, L. D. (2021). Cell Biology p53 and Tumor Suppression : It Takes a Network. Trends in Cell Biology, 31(4), 298–310. https://doi.org/10.1016/j.tcb.2020.12.011
  11. Chagas, C. M., Moss, S., & Alisaraie, L. (2018). Drug metabolites and their effects on the development of adverse reactions: Revisiting Lipinski’s Rule of Five. International Journal of Pharmaceutics, 549(1–2), 133–149. https://doi.org/10.1016/j.ijpharm.2018.07.046
  12. Chuang, C. H., Cheng, T. C., Leu, Y. L., Chuang, K. H., Tzou, S. C., & Chen, C. S. (2015). Discovery of akt kinase inhibitors through structure-based virtual screening and their evaluation as potential anticancer agents. International Journal of Molecular Sciences, 16(2), 3202–3212. https://doi.org/10.3390/ijms16023202
  13. Gu, X., Wang, Y., Wang, M., Wang, J., & Li, N. (2021). Computational investigation of imidazopyridine analogs as protein kinase B (Akt1) allosteric inhibitors by using 3D-QSAR, molecular docking and molecular dynamics simulations. In Journal of Biomolecular Structure and Dynamics (Vol. 39, Issue 1). https://doi.org/10.1080/07391102.2019.1705185
  14. Humaedi, A., Arsianti, A., & Radji, M. (2017). In Silico Molecular Docking Study of Gallic Acid and its Derivatives as Inhibitor BRAF Colon Cancer. International Journal of ChemTech Research, 10(1), 310–315.
  15. Humaedi, A., & Halimatushadyah, E. (2021). Computational Studies on The Relationship of the Activity of Gallic Acid Derivatives as Androgen Receptor Inhibitors in Prostate Cancer. Jurnal Biotek Medisiana Indonesia, 10(1), 65–76.
  16. Juhás, M., & Zitko, J. (2020). Molecular Interactions of Pyrazine-Based Compounds to Proteins. Journal of Medicinal Chemistry, 63(17), 8901–8916. https://doi.org/10.1021/acs.jmedchem.9b02021
  17. Kahkeshani, N., Farzaei, F., Fotouhi, M., Alavi, S. S., Bahramsoltani, R., Naseri, R., Momtaz, S., Abbasabadi, Z., Rahimi, R., Farzaei, M. H., & Bishayee, A. (2019). Pharmacological Effects of Gallic Acid In Health and Disease: A Mechanistic Review. Iranian Journal of Basic Medical Sciences, 22(3), 225–237. https://doi.org/10.22038/ijbms.2019.32806.7897
  18. Li, D., Wang, G., Jin, G., Yao, K., Zhao, Z., Bie, L., Guo, Y., Li, N., Deng, W., Chen, X., Chen, B., Liu, Y., Luo, S., & Guo, Z. (2019). Resveratrol suppresses colon cancer growth by targeting the AKT/STAT3 signaling pathway. International Journal of Molecular Medicine, 43(1), 630–640. https://doi.org/10.3892/ijmm.2018.3969
  19. Li, Z. J., Liu, M., Dawuti, G., Dou, Q., Ma, Y., Liu, H. G., & Aibai, S. (2017). Antifungal Activity of Gallic Acid In Vitro and In Vivo. Phytotherapy Research, 31(7), 1039–1045. https://doi.org/10.1002/ptr.5823
  20. Lin, X., Wang, G., Liu, P., Han, L., Wang, T., Chen, K., & Gao, Y. (2021). Gallic acid suppresses colon cancer proliferation by inhibiting SRC and EGFR phosphorylation. Experimental and Therapeutic Medicine, 21(6), 1–11. https://doi.org/10.3892/etm.2021.10070
  21. Nelson, V. kumar, Sahoo, N. K., Sahu, M., Sudhan, H. hara, Pullaiah, C. P., & Muralikrishna, K. S. (2020). In vitro anticancer activity of Eclipta alba whole plant extract on colon cancer cell HCT-116. BMC Complementary Medicine and Therapies, 20(1), 1–8. https://doi.org/10.1186/s12906-020-03118-9
  22. Nouri, A., Heibati, F., & Heidarian, E. (2021). Gallic Acid Exerts Nephroprotective, Anti-Oxidative Stress, and Anti-Inflammatory Effects Against Diclofenac-Induced Renal Injury in Malerats. Archives of Medical Research, 52(4), 380–388. https://doi.org/10.1016/j.arcmed.2020.12.005
  23. Pandurangan, A. K. (2013). Potential Targets for Prevention of Colorectal Cancer: a Focus on PI3K/Akt/mTOR and Wnt Pathways. Asian Pacific J Cancer Prev, 14(4), 2201–2205.
  24. Pant, V., & Lozano, G. (2014). Limiting the power of p53 through the ubiquitin proteasome pathway. Genes and Development, 28(16), 1739–1751. https://doi.org/10.1101/gad.247452.114
  25. Raghi, K. R., Sherin, D. R., Saumya, M. J., Arun, P. S., Sobha, V. N., & Manojkumar, T. K. (2018). Computational Study of Molecular Electrostatic Potential, Docking and Dynamics Simulations of Gallic acid derivatives as ABL inhibitors. Computational Biology and Chemistry, 74(3), 239–246.
  26. Rehan, M., Beg, M. A., Parveen, S., Damanhouri, G. A., & Zaher, G. F. (2014). Computational insights into the inhibitory mechanism of human AKT1 by an orally active inhibitor, MK-2206. PLoS ONE, 9(10), 18–22. https://doi.org/10.1371/journal.pone.0109705
  27. Revathidevi, S., & Munirajan, A. K. (2019). Akt in cancer: Mediator and more. Seminars in Cancer Biology, 59(6), 80–91. https://doi.org/10.1016/j.semcancer.2019.06.002
  28. Rezaei-Seresht, H., Cheshomi, H., Falanji, F., Movahedi-Motlagh, F., Hashemian, M., & Mireskandari, E. (2019). Cytotoxic activity of caffeic acid and gallic acid against MCF-7 human breast cancer cells: An in silico and in vitro study. Avicenna Journal of Phytomedicine, 9(6), 574–586. https://doi.org/10.22038/AJP.2019.13475
  29. Shah, H. D., Saranath, D., & Murthy, V. (2020). A molecular dynamics and docking study to screen anti-cancer compounds targeting mutated p53. Journal of Biomolecular Structure and Dynamics, 40(6), 2407–2416. https://doi.org/10.1080/07391102.2020.1839559
  30. Song, M., Bode, A. M., Dong, Z., & Lee, M. H. (2019). AKt as a therapeutic target for cancer. Cancer Research, 79(6), 1019–1031. https://doi.org/10.1158/0008-5472.CAN-18-2738
  31. Tabeshpour, J., Sahebkar, A., Zirak, M. R., Zeinali, M., Hashemzaei, M., Rakhshani, S., & Rakhshani, S. (2018). Computer-aided Drug Design and Drug Pharmacokinetic Prediction: A Mini-review. Current Pharmaceutical Design, 24(26), 3014–3019. https://doi.org/10.2174/1381612824666180903123423
  32. Variya, B. C., Modi, S. J., Savjani, J. K., & Patel, S. S. (2016). in Silico Molecular Docking and Pharmacokinetic Prediction of Gallic Acid Derivatives As Ppar-Γ Agonists. International Journal of Pharmacy and Pharmaceutical Sciences, 9(1), 102. https://doi.org/10.22159/ijpps.2017v9i1.15294
  33. Wang, R., Ma, L., Weng, D., Yao, J., Liu, X., & Jin, F. (2016). Gallic acid induces apoptosis and enhances the anticancer effects of cisplatin in human small cell lung cancer H446 cell line via the ROS-dependent mitochondrial apoptotic pathway. Oncology Reports, 35(5), 3075–3083. https://doi.org/10.3892/or.2016.4690
  34. Zhu, J., & Thompson, C. B. (2019). Metabolic regulation of cell growth and proliferation. Nature Reviews Molecular Cell Biology, 20(7), 436–450. https://doi.org/10.1038/s41580-019-0123-5