A series of novel thiosemicarbazone analogs (4a–t, 6a–j) were synthesized and evaluated for their cytotoxic activities. The obtained results showed that thiochromanone-based thiosemicarbazones substituted primarily at the C-8 position exhibited higher cytotoxicity than the corresponding 1,1-dioxo-thiochromanone-, benzothiazepine-, and 1,1-dioxo-benzothiazepine-based analogs. Significantly, compound 4c (8-fluoro thiochromanone thiosemicarbazone) was found to be the most active and exhibited potent cytotoxicity against the MCF-7, SK-mel-2, and DU145 cancer cell lines, with IC₅₀ values of 0.42, 0.58, and 0.43 µM, respectively. In addition, the mechanism of compound 4c induced MCF-7 cell apoptosis was preliminarily investigated through cell cycle, Annexin V-FITC/PI staining, and ROS assays, indicating that compound 4c may exert its anticancer property through ROS-mediated apoptosis.

中文翻译：

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硫代铬烷酮及其相关支架的硫代半咔唑衍生物的合成及抗癌活性

合成了一系列新型的硫半碳素类似物（4a – t，6a – j），并评估了它们的细胞毒性活性。获得的结果表明，主要在C-8位取代的基于噻吩并二氢噻吩酮的硫代半氨基甲酮显示出比相应的基于1，1-二氧代-噻吩并蒽醌，苯并噻氮酮和1，1-二氧代-苯并噻氮酮的类似物更高的细胞毒性。值得注意的是，发现化合物4c（8-氟硫代苯并二氢吡喃酮硫代半碳zone酮）对MCF-7，SK-mel-2和DU145癌细胞系最具活性，并显示出强大的细胞毒性，IC ₅₀值为0.42、0.58和分别为0.43 µM。另外，化合物4c的作用机理通过细胞周期，膜联蛋白V-FITC / PI染色和ROS分析初步研究了诱导的MCF-7细胞凋亡，表明化合物4c可能通过ROS介导的凋亡发挥其抗癌作用。