DFT and Molecular Docking Studies of N‐(7‐Indazolyl)benzenesulfonamides as Potential Drugs Targeting EGFR‐Tyrosine Kinase Inhibitors

Abstract

Abstract Compounds containing sulfonamides have a variety of biological activities, including an effect on anticancer receptors. This work reports the synthesis and anticancer risk assessment of several new N ‐(7‐indazolyl)benzenesulfonamides. These products have been used as precursors in various reactions to synthesize new N ‐(7‐indazolyl)benzenesulfonamides ( Bs‐1–6 ) starting with 7‐nitroindazole. Utilizing B3LYP/6–311 G (d,p) calculations based on the density functional theory (DFT), the global and local DFT‐based reactivity indices were analyzed. The calculated chemical shifts of 1 D NMR of N ‐(7‐indazolyl)benzenesulfonamides ( Bs‐1–6 ) were compared to the experimental values. Calculations have also been carried out to determine the nonlinear optical descriptors (NLO), such as the dipole moment, polarisability, and hyperpolarisability of both first and second‐order. In addition, a molecular docking study, ADMET analysis, MD simulation, and protein‐ligand distance analysis were carried out on the compounds to examine their interaction with the EGFR protease (PDB ID: 1m17). This comprehensive study highlights the potential of N ‐(7‐indazolyl)benzenesulfonamides as effective anticancer agents and provides valuable information for the future design of drugs targeting receptor tyrosine kinases.