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
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
复制标题
发现杨梅素是人 Flap 核酸内切酶 1 的有效抑制剂，可作为 HT-29 人结肠癌细胞的敏化剂
DOI：
10.1021/acs.jafc.8b05447
复制
发表时间：
2019-02-13
影响因子：
6.1
通讯作者：
Diao, Aipo
中科院分区：
文献类型：
--
作者：
Ma, Long;Cao, Xiuqi;Diao, Aipo
人瓣内切酶1(HFEN1)在DNA复制和修复中起重要作用。它能够切割由链置换反应产生的5‘单链突起(也称为5’瓣)。鉴于其重要的功能，hFEN1现在被认为是抗癌药物开发的DNA损伤反应系统中的一个重要靶点。在此，我们报道了杨梅素和一些天然黄酮类化合物能够抑制hFEN1。已经进行了构效关系、抑制机制、分子对接和基于癌细胞的分析。我们的原始发现扩大了类黄酮的活性，并可能为类黄酮辅助的靶向癌症治疗铺平道路。
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.