In silico study of Andrographolide from Andrographis paniculata (Burm F.) Ness as an anti-colorectal cancer agent

Milfa Viranti; Umi Baroroh; Dewi Astriany

doi:10.26905/jp.v21i1.13279

In silico study of Andrographolide from Andrographis paniculata (Burm F.) Ness as an anti-colorectal cancer agent

Milfa Viranti, Umi Baroroh, Dewi Astriany

Abstract

Cancer is one of the leading causes of death in the world, one of which is colorectal cancer, a malignant tumor in the epithelial tissue of the colon and rectum. Cancer treatment is long-term, so it has an impact on physical and psychological changes for patients. There was many exploration of anticancer drug candidates from natural ingredients such as andrographolide compounds. The in silico method can be done to predicts the absorption, distribution, metabolism, and excretion (ADME) of andrographolide compounds and meets Lipinski Rule of Five. The toxicity of andrographolide compounds was classified in class 4, which needs dose supervision. The prediction of activity potential is quite good based on the Structure-Activity Relationship (SAR). The results of molecular tethering of the three target receptors, namely Cyclooxigenase-2 (COX-2), caspase-3, and Vascular Endothelial Growth Factor Receptor-2 (VEGFR-2), showed that caspase-3 has the best binding value or affinity of -5.36 kcal/mol, with quite a lot of hydrogen bonds of 7. The amino acids formed in andrographolide compounds are the same as the baseline ligands, so it can be concluded that andrographolide has colorectal anticancer activity and can increase caspase-3 activity in colorectal cancer cells.

Keywords

Andrographolide, Cancer, Caspase-3, Molecular docking

Full Text:

PDF

References

Abdillah, M. N., Ilmah, N. R., & Mahardhika, A. B. (2018). penambatan molekuler senyawa polifenolat terhadap enzim reverse transcriptase sebagai senyawa antiretroviral (HIV-1). Jurnal Sains Dan Teknologi Farmasi Indonesia, 6(1), 1-13. http://dx.doi.org/10.58327/jstfi.v6i1.59

Dai, J., Lin, Y., Duan, Y., Li, Z., Zhou, D., Chen, W., Wang, L., & Zhang, Q. Q. (2017). Andrographolide inhibits angiogenesis by inhibiting the Mir-21-5p/TIMP3 signaling pathway. International Journal of Biological Sciences, 13(5), 660–668. https://doi.org/10.7150/ijbs.19194

Dekker, E., Tanis, P. J., Vleugels, J. L. A., Kasi, P. M., & Wallace, M. B. (2019). Colorectal cancer. Lancet, 394(10207), 1467–1480. https://doi.org/10.1016/S0140-6736(19)32319-0

Farooqi, A. A., Attar, R., Sabitaliyevich, U. Y., Alaaeddine, N., de Sousa, D. P., Xu, B., & C. Cho, W. (2020). The prowess of andrographolide as a natural weapon in the war against cancer. Cancers, 12(8), 2159. https://doi.org/10.3390/cancers12082159

Frimayanti, N., Lukman, A., & Nathania, L. (2021). Studi molecular docking senyawa 1,5-benzothiazepine sebagai inhibitor dengue DEN-2 NS2B/NS3 serine protease. Chempublish Journal, 6(1), 54–62. https://doi.org/10.22437/chp.v6i1.12980

Gadaleta, D., Vuković, K., Toma, C., Lavado, G. J., Karmaus, A. L., Mansouri, K., Kleinstreuer, N. C., Benfenati, E., & Roncaglioni, A. (2019). SAR and QSAR modeling of a large collection of LD50 rat acute oral toxicity data. Journal of Cheminformatics, 11(58), 1–16. https://doi.org/10.1186/s13321-019-0383-2

Grahl, M. V. C., Alcará, A. M., Perin, A. P. A., Moro, C. F., Pinto, É. S. M., Feltes, B. C., Ghilardi, I. M., Rodrigues, F. V. F., Dorn, M., da Costa, J. C., Norberto de Souza, O., & Ligabue-Braun, R. (2021). Evaluation of drug repositioning by molecular docking of pharmaceutical resources available in the Brazilian healthcare system against SARS-CoV-2. Informatics in Medicine Unlocked, 23, 100539. https://doi.org/10.1016/j.imu.2021.100539

Hussain, W., Qaddir, I., Mahmood, S., & Rasool, N. (2018). In silico targeting of non-structural 4B protein from dengue virus 4 with spiropyrazolopyridone: study of molecular dynamics simulation, ADMET and virtual screening. Virus Disease, 29(2), 147–156. https://doi.org/10.1007/s13337-018-0446-4

Kuipers, E. J., Grady, W. M., Lieberman, D., Seufferlein, T., Sung, J. J., Boelens, P. G., Van De Velde, C. J. H., & Watanabe, T. (2015). Colorectal cancer. Nature Reviews Disease Primers, 1, 1–51. https://doi.org/10.1038/nrdp.2015.65

Laksmiani, N. P. L., Reynaldi, K. R., Widiastari, M. I., Nugraha, I. P. W., Suyadnya, I. M. K., & Maharani, R. A. I. K. (2018). Cytotoxic activity of andrographolide in colon cancer through inhibition COX-2 by in silico study. Journal of Physics: Conference Series, 1040(1), 1–7. https://doi.org/10.1088/1742-6596/1040/1/012009

Laksmiani, N. P. L., Widiastari, M. I., & Reynaldi, K. R. (2017). Skrining potensi andrografolid dari Sambiloto (Andrographis paniculata (Burm F.) Ness.) sebagai antikanker payudara secara in silico. Jurnal Farmasi Udayana, 6(1), 50-54. http://dx.doi.org/10.24843/JFU.2017.v06.i01.p010

Li, L., Yang, L. L., Yang, S. L., Wang, R. Q., Gao, H., Lin, Z. Y., Zhao, Y. Y., Tang, W. W., Han, R., Wang, W. J., Liu, P., Hou, Z. L., Meng, M. Y., & Liao, L. W. (2022). Andrographolide suppresses breast cancer progression by modulating tumor-associated macrophage polarization through the Wnt/β-catenin pathway. Phytotherapy Research, 36(12), 4587–4603. https://doi.org/10.1002/ptr.7578

Lipinski, C. A., Lombardo, F., Dominy, B. W., & Feeney, P. J. (2012). Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. In Advanced Drug Delivery Reviews (Vol. 64, Issue SUPPL., pp. 4–17). https://doi.org/10.1016/j.addr.2012.09.019

Muchtaridi, M., Dermawan, D., & Yusuf, M. (2018). Molecular docking, 3D structure-based pharmacophore modeling, and ADME prediction of alpha mangostin and its derivatives against estrogen receptor alpha. Journal of Young Pharmacists, 10(3), 252–259. https://doi.org/10.5530/jyp.2018.10.58

Mutiah, R., Widyawaruyanti, A., & Sukardiman, S. (2015). Ekstrak etanol akar dan daun dari tanaman Calotropis gigantea aktif menghambat pertumbuhan sel kanker Kolon widr secara in vitro. Journal of Islamic Pharmacy, 1(1), 21-27. https://doi.org/10.18860/jip.v1i1.4278

Nur, S., Hanafi, M., Setiawan, H., Nursamsiar, N., & Elya, B. (2023). Molecular docking simulation of reported phytochemical compounds from Curculigo latifolia extract on target proteins related to skin antiaging. Tropical Journal of Natural Product Research, 7(11), 5067–5080. https://doi.org/10.26538/tjnpr/v7i11.9

Olaosebikan, O. J., Faboro, E. O., Fadare, O. A., & Ikotun, A. A. (2023). In silico investigation of the antimalarial activity of some selected alkaloids and terpenoids present in the aerial parts of Andrographis paniculata. Tropical Journal of Natural Product Research, 7(8), 3787–3799. https://doi.org/10.26538/tjnpr/v7i8.33

Pasha, A., Kumbhakar, D. V., Doneti, R., Kumar, K., Dharmapuri, G., Poleboyina, P. K., S. K., H., Basavaraju, P., Pasumarthi, D., S. D., A., Soujanya, P., Arnold Emeson, I., Bodiga, V., & Pawar, S. C. (2021). Inhibition of Inducible Nitric Oxide Synthase (iNOS) by andrographolide and in vitro evaluation of its antiproliferative and proapoptotic effects on cervical cancer. Oxidative Medicine and Cellular Longevity, 2021, 1–18. https://doi.org/10.1155/2021/6692628

Peng, Y., Wang, Y., Tang, N., Sun, D., Lan, Y., Yu, Z., Zhao, X., Feng, L., Zhang, B., Jin, L., Yu, F., Ma, X., & Lv, C. (2018). Andrographolide inhibits breast cancer through suppressing COX-2 expression and angiogenesis via inactivation of p300 signaling and VEGF pathway. Journal of Experimental and Clinical Cancer Research, 37(1), 1–14. https://doi.org/10.1186/s13046-018-0926-9

Ruswanto, R. (2015). molecular docking empat turunan isonicotinohydrazide pada mycobacterium tuberculosis enoyl-acyl carrier protein reductase (InhA). Jurnal Kesehatan Bakti Tunas Husada: Jurnal Ilmu-Ilmu Keperawatan, Analis Kesehatan Dan Farmasi, 13(1). http://dx.doi.org/10.36465/jkbth.v13i1.25

Supandi, Yeni, & Merdekawati, F. (2018). In silico study of pyrazolylaminoquinazoline toxicity by lazar, protox, and admet predictor. Journal of Applied Pharmaceutical Science, 8(9), 119–129. https://doi.org/10.7324/JAPS.2018.8918

Syahputra, G., Ambarsari, L., & Sumaryada, T. (2014). Simulasi docking kurkumin enol, bisdemetoksikurkumin dan analognya sebagai inhibitor enzim 12-Lipoksigenase. Jurnal Biofisika, 10(1), 55–67.

Veterini, L., Savitri, A. D., Widyaswari, M. S., Muhammad, A. R., Fairus, A., Zulfikar, M. Q. B., Astri, M., Ramasima, N. A., Anggraeni, D. P., & Nainatika, R. S. A. (2021). In silico study of the potential of garlic allicin compound as anti-angiogenesis in breast cancer. Tropical Journal of Natural Product Research, 5(11), 1995–1999. https://doi.org/10.26538/tjnpr/v5i11.17

Wanandi, S. I., Limanto, A., Yunita, E., Syahrani, R. A., Louisa, M., Wibowo, A. E., & Arumsari, S. (2020). In silico and in vitro studies on the anti-cancer activity of andrographolide targeting survivin in human breast cancer stem cells. PLoS ONE, 15(11), 1–19. https://doi.org/10.1371/journal.pone.0240020

Wu, Q. B., & Sun, G. P. (2015). Expression of COX-2 and HER-2 in colorectal cancer and their correlation. WJG: World Journal of Gastroenterology, 21(20), 6206–6214. https://doi.org/10.3748/wjg.v21.i20.6206

Zhang, Q., & Cui, Q. (2023). Target protein identification of andrographolide based on isomer approach. Journal of Pharmaceutical and Biomedical Analysis, 222, 115111. https://doi.org/10.1016/j.jpba.2022.115111

DOI: https://doi.org/10.26905/jp.v21i1.13279