Molecular Docking Study of Five Novel 1,2,3-Triazole Linked Metronidazole Derivatives as Cytotoxic Agents

Abstract

Background: Five novel synthetic 1,2,3-triazole-linked metronidazole compounds that target the tyrosine kinase of the epidermal growth factor receptor belong to the ErbB receptor family, which includes Her1 (EGFR), Her2 (erb-B2), Her3 (erb-B3), and Her4 (erb-B4). Certain human carcinomas, such as lung and breast cancer, feature cells that overexpress EGFR. This causes the anti-apoptotic Ras signaling cascade to be incorrectly activated, resulting in uncontrolled cell growth. Inhibiting EGFR TK (PDB code: 1M17) is an important target in the development of anticancer drugs since it can help prevent tumor growth and metastasis.

Materials and Methods: Using the molecular operating environment to evaluate the binding affinity of new design compounds against targeting proteins (EGFRTK). The molecular docking process predicts how molecules interact with the target enzyme, and criteria such as S-score and RMSD evaluate the docking outcomes by comparing estimated and experimental structures. It is an extremely useful tool for drug discovery and studying molecular interactions.

Results: The newly synthesized compounds (I-V) demonstrated improved binding energy (S.score) ranging from -7.5733 to -8.4456 Kcal/mol and reduced rmsd values ranging from 0.8752 to 1.6182 with the enzyme active site, as compared to erlotinib's binding energy of -7.7359 Kcal/mol and rmsd value of 1.720.

Conclusion: The docking results demonstrated that all synthesized compounds (I-V) had higher energy of binding (S-score) and lower Root Mean Square Deviation (RMSD) values, indicating theoretical potential as effective EGFR inhibitors when compared to the reference ligand (erlotinib)