Molecular Docking Simulation of Trisindolina 1 Compound Against Pi3k Protein in Hepatocellular Carcinoma

DOI

10.2991/absr.k.220406.038How to use a DOI?

Keywords

Apoptosis; Cancer; Docking; Hepar; PI3K; Trisindolina

Abstract

The increased cancer burden globally, from 12.7 million new cases in 2008 to a predicted 22.2 million in 2030, makes cancer a critical global problem with high unmet medical needs. Hepatocellular carcinoma (HCC) is the fifth most frequently diagnosed cancer worldwide, and HCC is the third leading cause of cancer death globally. One of the pathways that can affect liver cancer is apoptosis. Phosphatidylinositol 3-kinases (PI3Ks) are lipid kinases that play a central role in regulating apoptosis. Researchers worldwide have widely carried out research and development of natural ingredients as cancer therapeutic agents because natural ingredients are safer, cheaper, more effective, and have specific bioactive targets; they also have a few side effects. One example of a natural product is marine animals, namely sponges. Based on several studies, one of the natural ingredients with high potential as an anti-cancer is Trisindolina. Trisindolina 1 showed high cytotoxic activity on HepG2 cells with an IC50 value of 0.183 g/ml by apoptosis. The study aims to evaluate the antiproliferative activity and the mechanism, a PI3K inhibitor, and mechanism of action of a series of Trisindolina 1 as an anti-HCC agent. Then the underlying mechanism of Trisindolina 1 as the promising compound was evaluated using molecular docking. The type of research used is descriptive exploratory which is carried out through several stages, including data mining, ligand preparation, protein preparation, running docking, docking result validation, docking visualization, and data analysis. The result shows that the lowest docking score of the Trisindolina 1 ligand to the PI3K protein was -10.7 Kcal/mol while the Doxorubicin ligand score to the PI3K protein was -8.9 Kcal/mol. Trisindolina 1 can inhibit PI3K on some amino acids such as Met804 (Methionine number 804) and Met953 (Methionine number 953) through pi-sulfur bonds, Trp812 (Tryptophan number 812) through pi-sigma bonds, Pro810 (Proline number 810) via pi-alkyl bonds, Lys833 (Lysine number 883) through hydrogen bonds at the binding site. The biological activity of alkaloid compounds of PI3K protein can be through apoptosis in some pathways, such as PI3K.

Copyright

© 2022 The Authors. Published by Atlantis Press International B.V.

Open Access

This is an open access article distributed under the CC BY-NC 4.0 license.

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TY  - CONF
AU  - Evira Nadila Oktyasti
AU  - Awik Puji Dyah Nurhayati
PY  - 2022
DA  - 2022/05/02
TI  - Molecular Docking Simulation of Trisindolina 1 Compound Against Pi3k Protein in Hepatocellular Carcinoma
BT  - Proceedings of the 7th International Conference on Biological Science (ICBS 2021)
PB  - Atlantis Press
SP  - 268
EP  - 277
SN  - 2468-5747
UR  - https://doi.org/10.2991/absr.k.220406.038
DO  - 10.2991/absr.k.220406.038
ID  - Oktyasti2022
ER  -