Design and synthesis of N-aryl-2-trifluoromethyl-quinazoline-4-amine derivatives as potential Werner-dependent anticancer agents

Abstract

Abstract To discover new Werner (WRN) helicase inhibitors, a series of N-aryl-2-trifluoromethyl-quinazoline-4-amine derivatives were designed and synthesized through structural optimization strategy and the anticancer activities of 25 new target compounds against PC3, K562, and HeLa cell lines were evaluated by MTT assay. Some of it exhibited excellent inhibitory activity against three different cancer cells. In order to further verify whether the anticancer activity of these compounds is dependent on WRN, the PC3 cells with WRN overexpression (PC3-WRN) were constructed to further study their anticancer potence in vitro, the inhibition ratio and IC20 values showed that compounds 6a, 8i, and 13a were more sensitive to PC3-WRN than the control group cells (PC3-NC). The further study demonstrated that 13a was the most sensitivity in PC3-WRN among these tested compounds. In summary, our research provided a series of N-aryl-2-trifluoromethyl-quinazoline-4-amine derivatives as potential WRN-dependent anticancer agents.