ABSTRACT
In this study, twenty new anthranilic acid hydrazones 6-9 (a-e) were synthesized and their structures were characterized by Fourier-transform Infrared (FT-IR), Nuclear Magnetic Resonance (1 H-NMR - 13 C-NMR), and High-resolution Mass Spectroscopy (HR-MS). The inhibitory effects of the compounds against COX-II were evaluated. IC50 values of the compounds were found in the range of >200-0.32â µM and compounds 6e, 8d, 8e, 9b, 9c, and 9e were determined to be the most effective inhibitors. Cytotoxic effects of the most potent compounds were investigated against human hepatoblastoma (Hep-G2) and human healthy embryonic kidney (Hek-293) cell lines. Doxorubicin (IC50 : 8.68±0.16â µM for Hep-G2, 55.29±0.56â µM for Hek-293) was used as standard. 8e is the most active compound, with low IC50 against Hep-G2 (4.80±0.04â µM), high against Hek-293 (159.30±3.12), and high selectivity (33.15). Finally, molecular docking and dynamics studies were performed to understand ligand-protein interactions between the most potent compounds and COXâ II, Epidermal Growth Factor Receptor (EGFR), and Transforming Growth Factor betaâ II (TGF-ßII). The docking scores were calculated in the range of -10.609--6.705â kcal/mol for COX-II, -8.652--7.743â kcal/mol for EGFR, and -10.708--8.596â kcal/mol for TGF-ßII.