New Anthranilic Acid Hydrazones as Fenamate Isosteres: Synthesis, Characterization, Molecular Docking, Dynamics & in Silico ADME, in Vitro Anti‐Inflammatory and Anticancer Activity Studies

Abstract

AbstractIn 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 (1H‐NMR – 13C‐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 >200–0.32 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±0.16 μM for Hep‐G2, 55.29±0.56 μM for Hek‐293) was used as standard. 8e is the most active compound, with low IC50 against Hep‐G2 (4.80±0.04 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 COX II, Epidermal Growth Factor Receptor (EGFR), and Transforming Growth Factor beta II (TGF‐βII). The docking scores were calculated in the range of −10.609–−6.705 kcal/mol for COX‐II, −8.652–−7.743 kcal/mol for EGFR, and −10.708–−8.596 kcal/mol for TGF‐βII.