One-Pot Multicomponent Synthesis of Novel Thiosemicarbazone Derivatives Bearing Benzothiazole and Pyridine Moieties: Evaluated as Antineoplastic Agents by <i>In silico</i> and <i>In vitro</i>

A series of fused thiosemicarbazone derivatives bearing benzothiazole and pyridine moieties (MBK4-1 to MBK4-10) was synthesized using an efficient one-pot multicomponent approach, with sodium ascorbate as a green and effective catalyst, giving good to excellent yields. The structures were confirmed by IR, NMR, and MS analyses. The compounds were evaluated for anticancer activity against MCF-7, A-549, and HEP-G2 cell lines, where MBK4-6 showed the highest potency with IC50 values of 4.87, 3.74, and 2.07 µM, respectively. Molecular docking studies indicated strong binding interactions with key EGFR residues, and several derivatives showed better predicted affinity than erlotinib. In silico ADME analysis suggested favorable drug-likeness with high permeability, and good oral absorption. These findings highlight MBK4-6 as a promising lead for further anticancer development.