Synthesis and Computational Evaluation of Substituted Analogues of 4-Sulfonamide Phenylhydrazones as Potential Anticancer Agents: Molecular Docking, Physicochemical Properties, ADME-Tox, and DFT Analysis.

INTRODUCTION: Ten derivatives of benzenesulfonamide (SBB-1 to 10) have been synthesized via the condensation of terminal ketone and aldehyde with aromatic 4-sulfonamide phenylhydrazine. METHODS: 1H NMR, 13C NMR, IR, UV, and GC-MS were used to confirm the synthesized derivatives. The in vitro cytotoxicity of the synthesized sulfonamide derivatives SBB (1-10) was evaluated against the A549 human lung cancer cell line, using doxorubicin as the reference standard. RESULTS: The compound SBB-5 (IC50 16.36 ± 0.41 μM) demonstrated high anticancer potency due to the presence of a hydroxy group on the phenyl ring against all tested strains. DISCUSSION: The binding conformation of the most potent benzenesulfonamide (SBB-5) with the EGFR kinase (PDB code: 1M17) was ascertained by molecular docking studies. According to ADMET and DFT studies, the synthesized compounds showed favorable properties. CONCLUSION: Promising compounds like SBB-2, SBB-3, SBB-5, SBB-6, and SBB-7 exhibit favourable physicochemical properties, high drug-likeness, solubility, and a non-toxic profile, making them strong candidates for further development of a promising drug.