Docking Study of Selected Compounds Against Tyrosine Kinase Receptor for Cancer Treatment
Docking Study of Selected Compounds Against Tyrosine Kinase Receptor for Cancer Treatment
Mahdi Mohammadkhani,1,*Mohamadmahdi Zarei Gheshlagh,2Negar Alimohammadi,3Mohammadreza Hajipour,4Sepideh Haghighi Poodeh *,5
1. Department of Animal Biology, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran 2. Department of Cellular and Molecular Biology, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran 3. department of Biology, Central Tehran Branch, Islamic Azad University, Tehran, Iran 4. Department of Biology, Central Tehran Branch, Islamic Azad University, Tehran, Iran 5. Department of Convergent Sciences and Technologies, Central Tehran Branch, Islamic Azad University, Tehran, Iran
Introduction: Tyrosine kinases play a pivotal role in regulating various cellular processes, including signaling pathways, cell growth, and division. These enzymes are often found at elevated levels or exhibit heightened activity in certain cancer cells, making them critical targets for therapeutic intervention. Inhibition of tyrosine kinases has shown promising results in slowing down cancer progression and improving patient outcomes, as seen in chronic myeloid leukemia treatments.
This study focuses on the comparative analysis of five selected compounds known for their potential anticancer properties. These compounds include 6-Gingerol, Epigallocatechin Gallate (EGCG), Kaempferol, 6-Shogaol, and Chrysin, all of which have demonstrated anti-inflammatory, antioxidant, and anticancer activities through various biochemical pathways. By employing molecular docking techniques, we aim to evaluate the binding affinities and interaction profiles of these compounds with the tyrosine kinase receptor, with the goal of identifying the most potent inhibitor. The results of this study could provide valuable insights into the structure-activity relationships of these compounds, potentially guiding future drug development efforts.
Methods: The three-dimensional structures of the tyrosine kinase receptor and the five selected compounds were retrieved from the Protein Data Bank (PDB). Prior to molecular docking, the structures were prepared using ChemBioDraw and Chem3D software to ensure the accuracy of the molecular conformations. Molecular docking simulations were conducted using Chimera and AutoDock Vina, which enabled the identification of the optimal ligand-receptor conformations for each compound.
The docking analysis included the evaluation of binding modes, hydrogen bonding, and hydrophobic interactions between each compound and the tyrosine kinase receptor. To further validate the results, the Protein-Ligand Interaction Profiler (PLIP) was used to analyze the key interactions formed at the receptor's active site. The docking scores and binding energies obtained from Chimera and AutoDock Vina were used to rank the compounds according to their potential inhibitory effects on the tyrosine kinase receptor.
Results: Docking studies were performed on all selected compounds against the tyrosine kinase receptor. The results indicated that three of these compounds exhibit promising inhibitory potential against the target protein, showing favorable interactions such as hydrogen bonding, desolvation energy, optimal RMSD values, and stabilizing factors including salt bridges, hydrophobic interactions, π-stacking, and π-cation interactions.
Among the docked compounds, 6-Shogaol and Kaempferol demonstrated the lowest binding energies of -7.23 KJ/mol and -7.43 KJ/mol, respectively, indicating strong interactions with the protein target. On the other hand, EGCG, Chrysin, and 6-Gingerol showed binding energies of -8.5 KJ/mol, -7.5 KJ/mol, and -6.5 KJ/mol, respectively.
Despite its slightly higher binding energy, 6-Gingerol exhibited significant hydrogen bonding, which suggests a stable interaction with the receptor. This was considered an important factor in identifying it as a strong candidate for further study.
Conclusion: The docking study identified three compounds with significant inhibitory potential against the tyrosine kinase receptor. 6-Shogaol and Kaempferol emerged as top candidates due to their low binding energies, suggesting strong interactions with the protein target. However, 6-Gingerol was recognized for its hydrogen bonding interactions, which contribute to its stability despite a slightly higher binding energy. These findings ,similar to several studies provide a theoretical basis for the rational design of new pyrazole derivatives as potential cancer inhibitors, highlighting the potential for further development of targeted therapies against tyrosine kinase.