Potential of Indonesian Medicinal Plant Biodiversity as CHK1 Inhibitor Agent for Cancer Treatment by Bioinformatics and Computational Chemistry
Abstract
Indonesia is rich in flora diversity thanks to its biodiversity that has the potential as compounds that can be validated as candidate CHK1 inhibitor agents. The research was conducted in silico by performing molecular tethering using Autodock tools. The reference ligand was found from the 4FT3 receptor with the H1K code on the PDB. The result of docking in reference ligand obtained a Gibbs free energy value of -6.48 kcal/mol. The next process was carried out molecular tethering to 24 selected test compounds. The processes carried out are molecular docking, molecular visualisation, "Lipinski's Rule of Five" testing and Pre-ADMET testing. Based on Gibbs free energy, 18 molecules met the criteria and the best 3 were selected for analysis, namely stigmasterol, laurifolin, and quercetin with Gibbs free energy values of -10.40 kcal/mol, -8.70 kcal/mol, and -8.04 kcal/mol respectively. Based on the Pre-ADMET test, quercetin belongs to GSH toxicity class 4 which means the compound has a mild toxicity effect compared to other compounds. The molecular dynamics results showed that quercetin is the most stable compound and binds the longest compared to the others. The results can be continued for further research through laboratory testing stages in vitro and in vivo.
Keywords
Full Text:
PDFReferences
National Institutes of Health . (2011, 2 2). What is Cancer. Retrieved from National Cancer Institute: https://www.cancer.gov/publications/dictionaries/cancer-terms/def/parpinhibitor
Winarno, F. (1990). Teknologi pengolahan rumput laut / F.G. Winarno (Vol. 1). Jakarta, D.K.I Jakarta: Pustaka Sinar Harapan.
Podungge, A., Damongilala, L. J., & Mewengkang, H. W. (2018). KANDUNGAN ANTIOKSIDAN PADA RUMPUT LAUT Eucheuma spinosum YANG DIEKSTRAK DENGAN METANOL DAN ETANOL. Jurnal Media Teknologi Hasil Perikanan, 6(1).
A. N. Panche, A. D. (2016). Flavonoids: an overview. Journal of Nutritional Science.
Teoh, E. S. (2015). Secondary Metabolites of Plants. Medicinal Orchids of Asia.
Cancer.net. (2019, 2 28). Understanding Targeted Therapy. Retrieved from Cancer.Net:
https://www.cancer.net/navigating-cancer-care/how-cancer-treated/personalized-andtargeted-therapies/understanding-targeted-therapy
Torchilin, V. P. (2008, March 31). Cell Penetrating Peptide-Modified Pharmaceutical
Nanocarriers for Cell Penetrating Peptide-Modified Pharmaceutical Nanocarriers for Intracellular Drug and Gene Delivery. PeptideScience, 90(5), 604-610.
Shuguang Yuan, H. S. (2017). Using PyMOL as a platform for computational drug design.
Trott, O., & Olson, A. J. (2010). Software News and Update AutoDock Vina: Improving the Speed and Accuracy of Docking with a New Scoring Function, Efficient Optimization, and Multithreading. Journal of Computational Chemistry, 455-461.
Jumper, J., Evans, R., Pritzel, A., Green, T., Figurnov, M., Ronneberger, O., . . . Cowie, A. (2021, 7 15). Highly accurate protein structure prediction with AlphaFold. Nature, 596(7873), 583-589.
Daina, A., Michielin, O., & Zoete, V. (2017). SwissADME: a free web tool to evaluate pharmacokinetics, drug- likeness and medicinal chemistry friendliness of small molecules.
Scientific Reports, 42717.
Zeiger. (2010). Genetic Toxicology Testing. 139-158.
Yi-Hung Ou, P.-H. C.-P.-Y. (2005). p53 C-Terminal Phosphorylation by CHK1 and CHK2 Participates in the Regulation of DNA-Damage-induced C-Terminal Acetylation .
Molecular Biology of the Cell , 1684–1695.
Alindra Podungge, L. J. (2018). KANDUNGAN ANTIOKSIDAN PADA RUMPUT LAUT
EUCHEUMA SPINOSUM YANG DIEKSTRAK DENGAN METANOL DAN ETANOL.
Amberg, A. (2013). In Silico Methods. Drug Discovery and Evaluation: Safety and Pharmacokinetic Assays, 1273–1296. https://doi.org/10.1007/978-3-642-25240-2_55
Esaiyas, A., Mekonnen, Y., & Toeless, T. (2016). Hodge H. C. and Sterner J. H. (1949). “Tabulation of Toxicity Classes”, American Industrial Hygiene Association Quarterly, 10: 4, 93-96.. American Journal of Biomedical Research, 4(1). http://www.sciepub.com/reference/147273
Hollingsworth, S. A., & Dror, R. O. (2018). Molecular Dynamics Simulation for All. Neuron, 99(6), 1129–1143. https://doi.org/10.1016/j.neuron.2018.08.011
Jagdish Chander. (2018). Textbook of medical mycology. Jaypee Brothers Medical Publishers (P) Ltd.
Kozlíková, B., Krone, M., Lindow, N., Falk, M., Baaden, M., Baum, D., Viola, I., Parulek, J., & Hege, H.-C. (2015). Visualization of Molecular Structure: The State of the Art. Eurographics Conference on Visualization. https://www.cg.tuwien.ac.at/research/publications/2015/Viola_Ivan_2015_VBS/Viola_Ivan_2015_VBS-Paper.pdf
Lipinski, C. A., Lombardo, F., Dominy, B. W., & Feeney, P. J. (1997). Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Advanced Drug Delivery Reviews, 23(1-3), 3–25. https://doi.org/10.1016/s0169-409x(96)00423-1
Meng, X.-Y., Zhang, H.-X., Mezei, M., & Cui, M. (2011). Molecular Docking: A powerful approach for structure-based drug discovery. Current Computer-Aided Drug Design, 7(2), 146–157. https://www.google.com/url?q=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3151162/&sa=D&source=docs&ust=1665690286402435&usg=AOvVaw0f72qp7yxZ5KWjra8a9Qft
Pires, A. J. V., Gracia, R., & Valadares, S. C. (2004). Degradability of sugarcane bagasse treated with anhydrous ammonia and/or sodium sulfate. R. Bras. Zootec, 33(4), 1071–1077. https://www.feedipedia.org/node/4379
Sari, I. W., Junaidin, J., & Pratiwi, D. (2020). STUDI MOLECULAR DOCKING SENYAWA FLAVONOID HERBA KUMIS KUCING (Orthosiphon stamineus B.) PADA RESEPTOR α-GLUKOSIDASE SEBAGAI ANTIDIABETES TIPE 2. Jurnal Farmagazine, 7(2), 54. https://doi.org/10.47653/farm.v7i2.194
DOI: https://doi.org/10.24198/ijcb.v2i1.45150
Refbacks
- There are currently no refbacks.
This journal is indexed by :
Creative Commons Attribution :
Indonesian Journal of Computational Biology by Universitas Padjadjaran is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. Based on a work at http://jurnal.unpad.ac.id/ijcb/
Copyright © 2020 IJCB