Synthesis and molecular docking of some new thiazolidinone and thiadiazole derivatives as anticancer agents

New sets of functionalized thiazolidinone and thiadiazole derivatives were synthesized, and their cytotoxicity was evaluated on HepG2, MCF-7, HTC-116, and WI38 cells. The synthetic approach is based on the preparation of 4-(4-acetamidophenyl)thiosemicarbazide (4) and their thiosemicarbazones 5 a–e, which are converted to the corresponding thiazoldin-4-one compounds 6 a–e upon cyclization with ethyl bromoacetate. The thiadiazole compounds 9 and 12 were obtained by reacting 4-(4-acetamidophenyl)thiosemicarbazide with isothiocyanates and/or ethyl 2-cyano-3,3-bis(methylthio)acrylate, respectively. The thiazolidinone compounds 6 c and 6 e exhibited strong cytotoxicity against breast cancer cells, with an IC₅₀ (6.70±0.5 μM) and IC₅₀ (7.51±0.8 μM), respectively, very close to that of doxorubicin (IC₅₀: 4.17±0.2 μM). In addition, the anti-cancer properties of the tested thiazolidinone and thiadiazole scaffolds were further explored by the molecular docking program (MOE)-(PDB Code-1DLS). Compounds 5 d, 5 e, 6 d, 6 e, and 7 have the best binding affinity, ranging from −8.5386 kcal.mol⁻¹ to −8.2830 kcal.mol⁻¹.