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The potential of A. Muricata Bioactive Compounds to Inhibit HIF1α Expression Via Disruption of Tyrosine Kinase Receptor Activity: an In Silico Study

Firli Rahmah Primula Dewi, Rasyidah Fauzia Ahmar, Na’ilah Insani Alifiyah, Nadia Shoukat, Sri Puji Astuti Wahyuningsih.

Background: Cancer is a debilitating disease that is on the increase in both developed and developing countries. The plant extract of A. muricata have been known to have a variety of anticancer effects, including anti-angiogenic potential. An in silico study is needed as a preliminary study to understand the mechanism underline this process. Objective: The aim of this study was to investigate the potential of the bioactive compounds of A. muricata in regulating angiogenesis process, primarily by the regulation of hypoxia inducible factor (HIF)-1α expression by in silico study. Methods: This study was performed by in silico analysis including the bioactive compounds preparation, biological activity prediction, protein target and pathway analysis, 3D protein modelling, protein-ligand and protein-protein docking, and the visualization of docking results. Results: There are 3 bioactive compounds of A. muricata with the ability to inhibit HIF-1α expression, including kaempferol, genistein, and glycitein. The inhibition of HIF-1α expression was associated with phosphoinositide 3-kinases (PI3K)/Akt signaling pathway, which involved tyrosine kinase receptor activity on the cell membrane. Based on the silico analysis in this study, we shown that kaempferol, genistein, and glycitein inhibit HIF-1α expression through the disruption of interleukin (IL)-6R and toll-like receptor (TLR)-4 and their respective ligands interaction. Conclusion: The findings of this study show that A. muricata bioactive compounds could inhibit HIF-1α expression through disruption of the tyrosine kinase receptor binding with its ligand.

Key words: A. muricata, bioactive compounds, cancer, disease, in silico.

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The articles in Bibliomed are open access articles licensed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License (https://creativecommons.org/licenses/by-nc-sa/4.0/) which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.