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Discovery of Myricetin as a Potent Inhibitor of Human Flap Endonuclease 1, Which Potentially Can Be Used as Sensitizing Agent against HT-29 Human Colon Cancer Cells

Long Ma,Xiuqi Cao,Haiyue Wang,Kui Lu,Ying Wang,Chunhao Tu,Yujie Dai,Yuanyuan Meng,Yuyin Li,Peng Yu,Shuli Man,Aipo Diao

Human flap endonuclease 1 (hFEN1) is instrumental in DNA replication and repair. It is able to cleave the 5′ single-stranded protrusion (also known as 5′ flap) resulting from strand displacement reactions. In light of its crucial functions, hFEN1 is now deemed as a nontrivial target in the DNA damage response system for anticancer drug development. Herein, we report that myricetin and some natural flavonoids are able to inhibit hFEN1. Structure–activity relationship, inhibitory mechanisms, molecular docking, and cancer cell-based assays have been performed. Our original findings expand the activity of flavonoids and may pave the way for flavonoid-assisted targeted cancer therapy.