Abstract
A novel series of benzo[d]thiazole-2-carboxamide derivatives have been de novo designed based on virtual screening methods. The target compounds were synthesized and evaluated for the cytotoxicity against epidermal growth factor receptor high-expressed cancer cell lines (A549, HeLa, and SW480), epidermal growth factor receptor low-expressed cell line (HepG2) and human liver normal cell line (HL7702). Several target compounds have showed moderate to excellent potency against A549, HeLa, and SW480 and weak cytotoxic effects against HepG2, which implies they are probably epidermal growth factor receptor inhibitors. And scarcely did they exhibit any activities against HL7702, which signifies they are likely to overcome the nonspecific toxicity against normal cells. Especially, the compound 6-[2-(diethylamino)-2-oxoethoxy]-N-(furan-2-ylmethyl)benzo[d]thiazole-2-carboxamide (6i) was identified as a promising agent, exhibiting the most potent cytotoxic activities with IC50 values of 4.05, 12.17, 6.76 μM against the A549, HeLa, and SW480 cell lines, respectively.
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Acknowledgements
This work was supported by the National Science Foundation of China (NSFC) for the grant No. 21342006 and the Program for Innovative Research Team of the Ministry of Education of China for the grant No. IRT_14R36. The authors would like to thank Molegro ApS for kindly providing a free evaluation copy of their software package and Schrödinger, LLC for allowing the use of PyMOL Molecular Graphics System.
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Zhang, L., Deng, XS., Zhang, C. et al. Design, synthesis and cytotoxic evaluation of a novel series of benzo[d]thiazole-2-carboxamide derivatives as potential EGFR inhibitors. Med Chem Res 26, 2180–2189 (2017). https://doi.org/10.1007/s00044-017-1925-7
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DOI: https://doi.org/10.1007/s00044-017-1925-7