Affiliation:
1. Department of Chemistry Faculty of Science Mansoura University 35516 Mansoura Egypt
2. Department of Chemistry Faculty of Science Omar Al-Mukhtar University 919 El-Bayda Libya
3. Department of Chemistry College of Science King Saud University P.O. Box 2455 11451 Riyadh Saudi Arabia
4. Metabolic Biology & Biological Chemistry Department John Innes Centre, Norwich Research Park NR4 7UH Norwich UK
Abstract
AbstractNew 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.