Design, synthesis, molecular docking, and anticancer and antibacterial evaluation of new Schiff bases of thiadiazole derivatives targeting cellular mesenchymal-epithelial transition tyrosine kinase

Abstract

Several new nitrogenous heterocyclic Schiff base derivatives (2a-2e) were synthesized by the reaction of 5-amino-1,3,4-thiadiazole-2-thiol with various aldehydes. Molecular docking against cellular mesenchymal-epithelial transition tyrosine kinase demonstrated favorable binding interactions for the prepared compounds, where compound 2e exhibited the most favorable docking score of -12 (kcal/mol). The bioactivity of selected derivatives was also investigated. Compound 2b exhibited considerable cytotoxic activity against the hepatoblastoma G2 cell line with lower toxicity toward Human dermal fibroblasts, neonatal (HDFn) normal cells. Furthermore, compounds 2b and 2c possessed significant antibacterial activity against Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus, and Enterococcus faecalis. These findings suggest that thiadiazole-based Schiff bases may serve as promising candidates for further pharmaceutical investigations.. KEYWORDS :Schiff bases, 1,3,4-Thiadiazole, Cellular mesenchymal-epithelial transition tyrosine kinase, Molecular docking, Cytotoxicity assay.