Synthesis and biological evaluation of novel 5,6,7-trimethoxy flavonoid salicylate derivatives as potential anti-tumor agents

被引：13

作者：

Liu, Renbo ^{[1
,2
]}

Deng, Xiangping ^{[1
,2
]}

Peng, Yijiao ^{[1
]}

Feng, Wanshi ^{[1
]}

Xiong, Runde ^{[1
]}

Zou, Yang ^{[1
]}

Lei, Xiaoyong ^{[1
]}

Zheng, Xing ^{[1
]}

Xie, Zhizhong ^{[1
]}

Tang, Guotao ^{[1
,2
]}

机构：

[1] Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Inst Pharm & Pharmacol, Hengyang City, Peoples R China

[2] Hunan Prov Key Lab Tumor Microenvironm Respons Dr, Hengyang City, Hunan, Peoples R China

来源：

BIOORGANIC CHEMISTRY | 2020年 / 96卷

关键词：

Flavonoid; Anti-tumor; Microtubules; HIF-1; alpha; Glycolysis; GLUCOSE-METABOLISM; CANCER; HYPOXIA; CHRYSIN; DRUG; EXPRESSION; STRATEGIES; INHIBITORS; GROWTH; ACID;

D O I：

10.1016/j.bioorg.2020.103652

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

5,6,7-Trimethoxy flavonoid salicylate derivatives were designed by the joining of three important pharmaco-phores (TMP, flavonoid, and SA) according to the combination principle. A series of novel trimethoxy flavonoid salicylate derivatives were synthesized and their in vitro anti-tumor activities were evaluated. Among these derivatives, compound 7f exhibited excellent antiproliferative activity against HGC-27 cells and MGC-803 cells with IC50 values of 10.26 +/- 6.94 mu M and 17.17 +/- 3.03 mu M, respectively. Subsequently, the effects on cell colony formation (clonogenic survival assay), cell migration (wound healing assay), cell cycle distribution (PI staining assay), cell apoptosis (Hoechst 33258 staining assay and annexin V-FITC/PI dual staining assay), lactate level (lactate measurement), microtubules disarrangement (immunofluorescence staining analysis) and docking posture (molecular docking simulation) were determined. Further western blot analysis confirmed that compound 7f could effectively down-regulate the expression of glycolysis-related proteins HIF-1 alpha, PFKM and PKM2 and tumor angiogenesis-related proteins VEGF. Overall, these studies suggested that compound 7f, as the representative compound of those, might be a promising candidate for the treatment of gastric cancer and deserved the further studies.

引用

页数：15

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