Design,Synthesis and Antitumor Activity of FAK/PLK1 Dual Inhibitors with Quinazolinone as the Skeleton |
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Authors: | Juan Sun Ze-Yu Fang Yi-Nuo Tao Yi-Heng Zhang Yao Zhang Hai-Ya Sun Yang Zhou Yuan-Feng Wu |
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Affiliation: | 1. School of Biological & Chemical Engineering, Zhejiang University of Science & Technology, Hangzhou, 310023 P. R. China;2. Zhejiang Engineering Research Center for Biomedical Materials, Cixi Institute of Biomedical Engineering, Ningbo Institute of Materials Technology and Engineering, Chinese Academy of Sciences, Ningbo, 315300 P. R. China |
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Abstract: | Febrifugine is a kind of quinazolinone compound with high biological activity from a Chinese herb called Chang Shan (Dichroa febrifuga). Febrifugine and its derivatives possess extensive biological activities, some of which exhibited anti-tumor activities as FAK inhibitors. However, they are not very effective at inhibiting tumor metastasis, perhaps because tumors gain energy through compensatory activation of other signaling pathways that promote cell migration and invasion. Therefore, seventeen novel febrifugine derivatives with quinazolinone skeleton were designed, synthesized and acted as potential FAK/PLK1 dual inhibitors. These compounds were determined by 1H-NMR, 13C-NMR and MS. Most of the compounds exhibited good inhibitory activity against cancer cell lines by computer-assisted screening, antitumor activity test and FAK/PLK1 inhibitory activity test, wherein compound 3b was screened as a high-efficiency lead compound. |
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Keywords: | febrifugine molecular docking quinazolinone FAK/PLK1 antitumor |
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