A novel series of 1-(5-(benzylthio)-1,3,4-thiadiazol-2-yl)-3-phenylurea derivatives (5a–l) were designed and synthesized as sorafenib analogs. The in vitro cytotoxicity effects of synthesized compounds were evaluated against four different human cancer cells including MCF-7, HepG2, A549, and HeLa cell lines. The biological results showed that most of the compounds significantly prevented the proliferation of tested cancer cells. In particular, 2-F, 4-Cl, and 2,6-diF substituted derivatives (5d, 5g, and 5k) showed promising activities, especially against Hela cancer cells (IC₅₀ = 0.37, 0.73 and 0.95 µM, respectively) which were significantly more potent than sorafenib as the reference drug (IC₅₀ = 7.91 µM). Flow cytometry analysis revealed that the prototype compounds (5d, 5g, and 5k) significantly induced apoptotic cell death in HeLa cancer cells and blocked the cell cycle at the sub-G1 phase. Moreover, in silico docking study confirmed the binding of the prototype compound to the active site of VEGFR-2.

设计并合成了一系列新型的1-（5-（苄硫基）-1,3,4-噻二唑-2-基）-3-苯基脲衍生物（5a-1）作为索拉非尼类似物。评价了合成化合物对四种不同的人类癌细胞（包括MCF-7，HepG2，A549和HeLa细胞系）的体外细胞毒性作用。生物学结果表明，大多数化合物显着阻止了测试癌细胞的增殖。特别是2-F，4-Cl和2,6- di F取代的衍生物（5d，5g和5k）显示出有希望的活性，尤其是针对Hela癌细胞（IC ₅₀ 分别为0.37、0.73和0.95 µM），这比索拉非尼作为参考药物的效用要强得多（IC ₅₀  = 7.91 µM）。流式细胞仪分析表明，原型化合物（5d，5g和5k）显着诱导HeLa癌细胞凋亡，并阻止了亚G1期的细胞周期。此外，计算机对接研究证实了原型化合物与VEGFR-2活性位点的结合。