Research Information System
ChemistrySelect, vol.10, no.37, 2025 (SCI-Expanded)
The search for new anticancer agents targeting key signaling pathways, such as the extracellular signal-related kinase 2 pathway (ERK2), is of utmost importance. In this study, a sulfonamide derivative, 5-fluoro-2-(methylamino)benzenesulfonamide (SA), was synthesized and tested as a potential ERK2 inhibitor for treating non-small cell lung cancer. An integrated approach combining in silico methods (ADMET, molecular docking, molecular dynamics) and in vitro assays (MTT cytotoxicity, wound healing) on the A549 lung cancer cell line was used. ADMET predictions indicated that SA has a favorable pharmacokinetic and safety profile, consistent with Lipinski's rule. Molecular docking revealed a stronger binding affinity for SA (−91.213 kcal/mol) compared to doxorubicin (−86.198 kcal/mol) and the native ligand, catechol. The 100 ns molecular dynamics simulations confirmed the stability of the SA-ERK2 complex. Biologically, SA showed moderate, dose-dependent cytotoxicity against A549 cells, with an IC50 of 57.80 µM at 48 h, and notably inhibited cell migration. Overall, these findings suggest that compound SA is a promising lead for developing new, more potent sulfonamide derivatives targeting ERK2 in lung cancer treatment.