Thymol-1,2,3-triazole derivatives: Network pharmacology, molecular simulations and synthesis targeting breast cancer

•A series of 1,2,3-triazole derivatives tethered to p-methoxythymol, a natural product was synthesized and further elucidated by detailed analysis of their HRMS, ¹H- and ¹³CNMR spectra.•Molecular docking results were further validated and refined through molecular dynamic (MD) simula.•Network pharmacology screening identifies potential targets for cancer treatment. Cancer prevention has become a major focus of public health in the 21st century. Despite advancements in treatment, tackling cancer remains a significant challenge due to the different types of cancer. Breast cancer stands out as the leading cause of cancer-related deaths, highlighting its significant impact on female health worldwide. Monoterpenes, exemplified by thymol, exhibit notable potential in cancer treatment, owing to their pharmacological properties and mechanisms of action. Concurrently, 1,2,3-triazoles have garnered attention as promising entities for the development of anticancer agents, showcasing their efficacy and relevance in oncology research. This study describes the synthesis and characterization of a novel library of 1,2,3-triazole derivatives tethered to p-methoxythymol, a natural product. High-resolution mass spectrometry (HRMS) definitively confirmed the structures of the synthesized compounds, which were further elucidated by detailed analysis of their ¹H- and ¹³CNMR spectra. To predict the suitable target, network pharmacology was applied to the synthesized thymol derivatives, resulting in the identification of phosphatidylinositol-3-kinase (PIK3CA) as a key target. Furthermore, these thymol derivatives were screened for ADMET and molecular docking against the phosphatidylinositol-3-kinase (PIK3CA) target. Molecular dynamics simulations were conducted for the top two compounds over a duration of 100 ns to assess their stability. The RMSD (Root-Mean-Square Devia­tion) and RMSF (root-mean-square fluctuation) values for amino acid residues indicated structural integrity and stable protein-ligand interaction. Additionally, all designed compounds displayed favorable physicochemical properties and ADMET profiles, and two compounds, 4b and 4d, were found to be new lead molecules targeting PIK3CA [Display omitted]