Design, Synthesis, Characterization, Integrated SAR and Molecular Docking Studies of Sulphonamide-Derived Indole-2-one Schiff's Baseas Potential Anticancer and Antibacterial Agent

AbstractIndole-2,3-dione (isatin) and its derivatives have gained considerable attention owing to theirbroad spectrum of biological activities, particularly anticancer and antibacterial properties. Inview of the increasing resistance to existing antimicrobial agents and the urgent need fornovel anticancer therapeutics, the present study focuses on the synthesis, characterization,and biological evaluation of a series of novel sulphonamide-containing indole-2-one Schiff’sbases (7a–7j). The synthesized compounds were evaluated for their antibacterial activityagainst Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli)bacteria, as well as for anticancer activity against human cancer cell lines. Compounds 7a, 7c,and 7j exhibited significant antibacterial activity, while compounds 7b and 7c demonstratedacceptable anticancer activity; the remaining derivatives showed moderate biologicalefficacy. To further understand the binding interactions and possible mechanism of action,molecular docking studies were carried out using the Schrödinger Suite. Compound 7bdisplayed a high docking score of −9.729 with a binding energy of −42.828 kcal/mol,whereas compounds 7c, 7e, and 7j also exhibited strong binding affinities with dockingscores of −9.238, −8.438, and −9.823, respectively, outperforming the standard drug. The docking scores of the newly developed compounds ranged from −8.512 to −3.142. Hydrogen-bond interactions were limited and observed primarily for compounds 7e (GLY 521), 7l (LEU 525), 7j (ASP 351), and 7f (ASP 351), while significant hydrophobic interactionsinvolving residues ARG 394 and TRP 383 contributed to ligand stabilization for several compounds. Overall, the combined biological and in silico results suggest that sulphonamide-based indole-2-one Schiff’s bases represent promising lead structures for the development of novel antibacterial and anticancer agents.