Abstract
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.
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This work was supported and funded by National Institute for Medical Research Development (NMIAD) Grant no. 963529.
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Aghcheli, A., Toolabi, M., Ayati, A. et al. Design, synthesis, and biological evaluation of 1-(5-(benzylthio)-1,3,4-thiadiazol-2-yl)-3-phenylurea derivatives as anticancer agents. Med Chem Res 29, 2000–2010 (2020). https://doi.org/10.1007/s00044-020-02616-2
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DOI: https://doi.org/10.1007/s00044-020-02616-2
Keywords
- 1,3,4-Thiadiazole
- Anticancer
- Sorafenib
- Cytotoxic activity