Biological evaluations and computational studies of newly synthesized thymol-based Schiff bases as anticancer, antimicrobial and antioxidant agents.

Three new thymol-based molecules were synthesized and evaluated as anticancer, antimicrobial and antioxidant agents. Liver, colon, lung and prostate cancer cell lines were utilized in cytotoxicity tests. The results demonstrated that synthesized molecules had a cytotoxic effect against the screened cell lines. One of the molecules (4a) was found to have a higher efficacy towards the colon cancer cell line (DLD-1) with an IC₅₀ value of 12.39 µM and the other (4c) towards the prostate cancer cell line (PC3) with an IC₅₀ value of 7.67 µM than the positive control drug cisplatin. To assess the antimicrobial activity of molecules (4a-c), Gram-positive bacteria, Gram-negative bacteria and yeast were subjected to agar disc diffusion and broth microdilution assays. The investigation of antioxidant potential was conducted using the DPPH radical scavenging activity assay. While all compounds displayed strong cytotoxic and antioxidant properties, they exhibited only moderate antimicrobial activity. Molecular docking studies were performed on epidermal growth factor receptor (EGFR), vascular endothelial growth factor receptor 2 (VEGFR-2), focal adhesion kinase (FAK), B-Raf and phosphoinositide 3-kinase (PI3K). The binding energies and interactions obtained from the docking results of compounds (4a-c) supported the experimental results. Drug similarity rates and pharmacokinetic properties were analyzed with the absorption, distribution, metabolism and excretion (ADME) method. Geometric parameters such as chemical potential (µ), electrophilicity index (ω) and chemical softness (σ) of compounds (4a-c) were calculated using the 6-31*G basis set B3LYP method.