Novel Imino Derivatives of Thymol: Synthesis, in vitro Cytotoxic Activities, Molecular Docking Analysis and ADME Prediction

Cancer is a significant global health challenge that affects millions of individuals every year. The development of new anticancer drugs is imperative to address the issue of drug resistance in cancer therapy. Therefore, in this study, novel imino derivatives of thymol (3a-c) were synthesized and evaluated as anticancer agents. These compounds were structurally elucidated using elemental analysis and various spectroscopic methods, including 1H and 13C Nuclear Magnetic Resonance (NMR) and Fourier Transform Infrared Spectroscopy (FT-IR). The cytotoxic activities of the new compounds on human liver cancer (HepG2) and healthy human kidney (HEK-293T) cell lines were investigated. Compounds were tested at various concentrations to determine their IC50 values. Among the tested new compounds, 3a and 3b demonstrated cytotoxicity in HepG2, with IC50 values of 88.97 µM and 106.10 µM, respectively. Furthermore, compound 3a also exhibited significant toxicity against the HEK-293T cell line, suggesting that further modifications are needed to improve selectivity for healthy cells. ADME properties analysis resulted in the detection of two lead compounds (3a and 3b) among compounds 2a-c and 3a-c. For the most active compounds 3a and 3b, molecular docking study on epidermal growth factor tyrosine kinase receptor (PDB ID: 3POZ), PI3K alpha (PDB ID: 4FA6), c-kit tyrosine kinase (PDB ID:1T46) was performed to verify the in vitro experimental results. © The Tunisian Chemical Society and Springer Nature Switzerland AG 2026.