Mechanism Analysis of Artemisinin and Artesunate as Lung Cancer Therapy Agents Through in Silico Method

Abstract

Several in vitro studies have focused on the ability of artemisinin and its derivatives to suppress lung cancer cells, but there are still many biological processes and mechanisms, such as the interactions between the active compounds (ligands) and receptors that are not well understood and require further research. Drug targeting for lung cancer will be more precise and the inhibition of cancer cell proliferation will be increased as a result of understanding the mechanism of interaction between artemisinin and its derivatives with lung cancer receptors. Currently, there are no studies that report the interaction between artemisinin and its derivatives with the PARP1 receptor. The results of this study will offer one recommendation and a description of how artemisinin and its derivatives interact with the PARP1 receptor when used as an in silico lung cancer therapeutic agent. This study attempts to uncover and understand the interactions between the active compounds artemisinin and its derivatives and receptors involved in lung cancer cell proliferation by using molecular docking and Molecular Dynamics methods. The molecular docking simulation is an in silico analysis technique that uses a computer to give an overview of how a chemical interacts as a ligand with proteins or receptors in drug discovery studies. Utilizing molecular dynamic simulation, the stability of the binding relationship between the ligand and receptor will be assessed over a specific amount of time. Autodock vina was used for molecular docking simulation. The receptor was taken from the protein database with PDB ID: 7KK6 (PARP1). Molecular Dynamic (MD) simulation using GROMACS 2023 for 100 ns. Interpretation of molecular docking results is shown as affinity values, while the MD results are displayed as RMSD graphs. The binding affinity value can determine the PARP1 receptor and ligand interactions. Low binding affinity values indicate that the protein and ligand binding interactions are becoming more stable. The results of molecular docking showed that artesunate had the most negative binding affinity value of -8.9 kcal/moL, the original ligand (veliparib) was -8.8 kcal/moL, and artemisinin -8.5 kcal/moL, which means that artesunate has the ability binding and mechanism of action similar to veliparib. The RMSD value can be used to assess the binding stability that artemisinin and artesunate create with the PARP1 receptor. RMSD PARP1 with Veliparib has a value of 0.16 nm, while RMSD PARP1 values when interacting with Artesunate and artemisinin are 0.19 and 0.18 nm, respectively. Based on RMSD values and molecular interactions during MD simulations, PARP1 has the same stability when interacting with artesunate, artemisinin, and veliparib. There are similar interactions between veliparib and artesunate and PARP1 is a receptor engaged in the interaction between artemisinin and artesunate on the proliferation of lung cancer cells. Interaction between PARP1 with veliparib and artesunate showed a stable interaction during molecular dynamics simulations. Apart from normal cells, PARP1 also plays a role in cell cancer. Cancer cells that have been treated with chemotherapy and radiation will make an effort to repair their DNA utilizing PARP1. This situation allows PARP1 to be a target for anticancer treatment.