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

发现杨梅素是人类瓣膜内切酶 1 的有效抑制剂,可能可用作针对 HT-29 人类结肠癌细胞的敏化剂

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

Abstract

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.

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