Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
Genetics Department, Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, Iran.
Bioorg Chem. 2021 Mar;108:104553. doi: 10.1016/j.bioorg.2020.104553. Epub 2020 Dec 13.
A series of quinazolin-4(3H)-one based agents containing thiadiazole-urea were designed, synthesized, and biologically evaluated. The proliferation rate of PC3 cells was moderately reduced by compound 9f (IC = 17.7 μM)which was comparable with sorafenib (IC = 17.3 μM). There was also a significant reduction in the number of HUVEC cells, when they were exposed to compound 9y (IC = 6.1 μM). To test the potential of compounds in inducing apoptosis, Annexin V-FITC/propidium iodide double staining assay was used. After the treatment of HUVEC cells with 9f, they underwent apoptotic effects. A substantial effort was dedicated to gathering comprehensive data across CAM assay. These data showed that 9f moderately inhibits the growth of corresponding blood vessels. Finally, the outcomes of Western blotting proposed a mechanism of action, by which the phosphorylation of VEGFR-2 is inhibited by compounds 9f and 9y.
设计、合成并生物评价了一系列含噻二唑脲的喹唑啉-4(3H)-酮类化合物。化合物 9f（IC=17.7μM）能中度抑制 PC3 细胞的增殖率，与索拉非尼（IC=17.3μM）相当。化合物 9y（IC=6.1μM）能显著减少 HUVEC 细胞的数量。为了检测化合物诱导细胞凋亡的潜力，采用 Annexin V-FITC/碘化丙啶双染色法进行检测。用 9f 处理 HUVEC 细胞后，它们发生了凋亡效应。我们还进行了全面的 CAM 试验来获取综合数据。这些数据表明，9f 能适度抑制相应血管的生长。最后，Western blot 的结果提出了一种作用机制，即化合物 9f 和 9y 抑制 VEGFR-2 的磷酸化。
