Department of Chemistry, Faculty of Science, Mansoura University, 35516, Mansoura, Egypt.
Department of Chemistry, Faculty of Science, Omar Al-Mukhtar University, 919, El-Bayda, Libya.
Chem Biodivers. 2024 Jul;21(7):e202301870. doi: 10.1002/cbdv.202301870. Epub 2024 Jun 25.
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 IC (6.70±0.5 μM) and IC (7.51±0.8 μM), respectively, very close to that of doxorubicin (IC: 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 to -8.2830 kcal.mol.
新的一系列功能化噻唑烷二酮和噻二唑衍生物被合成，并在 HepG2、MCF-7、HTC-116 和 WI38 细胞上评估其细胞毒性。该合成方法基于制备 4-(4-乙酰氨基苯基)硫代半卡巴肼(4)及其硫代腙 5a-e，它们与溴乙酸乙酯环化得到相应的噻唑烷-4-酮化合物 6a-e。噻二唑化合物 9 和 12 通过与异硫氰酸酯和/或乙基 2-氰基-3,3-双(甲硫基)丙烯酸酯反应得到。噻唑烷二酮化合物 6c 和 6e 对乳腺癌细胞表现出很强的细胞毒性，其 IC(6.70±0.5 μM)和 IC(7.51±0.8 μM)非常接近阿霉素(IC: 4.17±0.2 μM)。此外，通过分子对接程序(MOE)-(PDB 代码-1DLS)进一步探索了测试的噻唑烷二酮和噻二唑支架的抗癌特性。化合物 5d、5e、6d、6e 和 7 具有最佳的结合亲和力，范围从-8.5386 kcal.mol 到-8.2830 kcal.mol。
