Synthesis, spectroscopic analysis, molecular docking and DFT study of novel 1,2,3-Triazole derivatives incorporating paramethoxythymol and salicylaldehyde moieties

This study investigates the synthesis, characterization, and computational analysis of novel paramethoxythymol-1,2,3-triazole derivatives derived from naturally occurring thymol. HRMS and NMR spectroscopy (¹H and ¹³C) were meticulously employed to ensure precise identification of the synthesized compounds. Density functional theory (DFT) calculations were performed to elucidate the stability of the derivatives. In silico docking simulations, molecular dynamics, and ADMET analysis provided insights into the potential interactions between the synthesized molecules and the active sites of Epidermal Growth Factor Receptor (EGFR) and B-cell lymphoma 2 (Bcl2). Docking analysis revealed favorable binding affinities of the 1,2,3-triazole derivatives towards EGFR, with compound 5b exhibiting the most potent interaction, characterized by a docking score of -28.8 kJ/mol. Conversely, compound 6b demonstrated a docking score of -29.2 kJ/mol with Bcl2. Molecular dynamics investigations indicated that the complex between Bcl2 and compound 5b is more stable, suggesting it as a potential candidate for inhibiting Bcl2 protein. These findings suggest that paramethoxythymol-1,2,3-triazole derivatives hold promise as lead candidates for the development of novel targeted anticancer agents.