Design, synthesis, and multitarget evaluation of thiosemicarbazone–sulfonamide hybrids as potent cholinesterase and MAO-A inhibitors with neuroblastoma-associated cytotoxicity

of 5.23 µM and a selectivity index of 8.6 relative to HUVEC cells. Molecular docking and MM-GBSA analyses revealed strong binding affinities (docking scores - 10.4 to - 15.4 kcal/mol; ΔG_bind - 55.9 to - 88.4 kcal/mol), which were further supported by molecular dynamics simulations. DFT calculations indicated favorable electronic properties (HOMO-LUMO gap: 0.098-0.116 eV), while ADME predictions suggested acceptable drug-like behavior and good oral absorption. These results identify thiosemicarbazone derivative 5n as a promising multitarget lead for the development of agents targeting cholinergic dysfunction, MAO-A inhibition, and neuroblastoma proliferation.