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INTERNATIONAL CONGRESS OF

CancerGenetics

• Inhibitory Study of Thyme and Garlic Extracts on Key Receptors in Inflammation and Cancer with a Bioinformatics Approach

• Parichehr Ebrahimi Shahabadi,^1,* Mohammad Ali Nazmabadi Nezhad,²
  1. Doctorate of Veterinary Medicine Graduated, Faculty of Veterinary Medicine, Shahid Bahonar University of Kerman, Kerman, Iran
  2. Doctorate of Veterinary Medicine Graduated, Faculty of Veterinary Medicine, Shahid Bahonar University of Kerman, Kerman, Iran
  
  
  
• Introduction: Increasing drug resistance and side effects caused by long-term use of chemical drugs have led researchers to discover natural compounds with high efficiency and less toxicity. Thyme (Thymus vulgaris) and garlic (Allium sativum) have long been known in traditional medicine as plants with anti-inflammatory and anticancer properties; however, the exact molecular mechanism of these effects has not been fully explained. This study aims to bioinformatically evaluate the potential of active compounds present in thyme extract (thymol) and garlic (allicin and similar sulfur compounds) in inhibiting two key receptors involved in inflammatory and tumor pathways, including cyclooxygenase-2 (COX-2) and epidermal growth factor receptor (EGFR).
• Methods: This study was a computational study based on molecular docking and molecular dynamics simulation. In the first step, the 3D structures of the main compounds of thyme (thymol) and garlic (allicin, diallyl disulfide, and other sulfur compounds) were obtained from the PubChem database. The 3D structures of the target receptors, including COX-2 and EGFR, were also downloaded from the Protein Data Bank (RCSB PDB). Protein preparation was performed by removing excess water molecules, adding hydrogen atoms, and optimizing the force field using standard bioinformatics software. Molecular docking was performed using the Lamarckian genetic algorithm in the AutoDock Vina software. The dimensions of the search grid were determined based on the active site coordinates of each receptor reported in authoritative reference articles. Each docking process was performed in three separate iterations, and the best complexes were selected based on the lowest binding free energy as well as the pattern of molecular interactions, including hydrogen bonds and hydrophobic interactions. In the next step, for the selected complexes, molecular dynamics simulations were performed using GROMACS software and a standard force field under simulated physiological conditions (temperature 310°K and pressure 1 bar) for a sufficient time to achieve system stabilization. Key stability parameters, including root mean square deviation (RMSD), root mean square fluctuation (RMSF), and radius of gyration (Rg), were analyzed and investigated throughout the simulation.
• Results: Molecular docking results showed that thymol from thyme has a significant and favorable affinity for the COX-2 receptor, and its binding pattern closely resembles the binding site of standard anti-inflammatory drugs such as celecoxib and ketoprofen. A detailed study of molecular interactions indicated that thymol can effectively inhibit COX-2 activity by forming stable hydrogen bonds with key amino acids of the enzyme active site, as well as numerous hydrophobic interactions. In the case of the EGFR receptor, which plays a pivotal role in the proliferation of cancer cells, especially in lung cancer, sulfur compounds in garlic, including allicin, diallyl disulfide, and diallyl trisulfide, were able to bind with good affinity to the tyrosine kinase binding site of this receptor. Molecular dynamics simulation results for the thymol-COX-2 complex indicated very good stability of the complex over the simulation time; So that after the initial phase, the RMSD value reached a stable platform and the fluctuations of amino acids in the binding site were limited and insignificant, indicating a strong and irreplaceable binding of the ligand. Also, the simulation of the allicin complex with the EGFR receptor showed acceptable stability, and the average RMSD remained in a stable range, indicating the preservation of the functional three-dimensional structure of the protein in the presence of the ligand. The radius of gyration also remained in its desired range in both complexes, which confirms the compactness and structural stability of the ligand-protein complexes. In addition, the studies conducted showed that the studied compounds all have desirable pharmacological properties and satisfy the Lipinski rules (rule of five) defined for oral drugs.
• Conclusion: The present study, using bioinformatics tools including molecular docking and molecular dynamics simulation, showed that the main compounds in thyme extract (especially thymol) and garlic (especially allicin and other sulfur compounds) can bind effectively, stably, and specifically to the active sites of key inflammatory (COX-2) and tumor (EGFR) receptors. These findings, which are also consistent with the evidence in authoritative articles, provide a detailed molecular mechanism for the anti-inflammatory and anticancer effects reported for these plants in traditional medicine.
• Keywords: Molecular docking, thyme, garlic, bioinformatics, natural inhibitors