Design, Synthesis and Antitumor Activity of FAK/PLK1 Dual Inhibitors with Quinazolinone as the Skeleton

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 1 H‐NMR, 13 C‐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.