Discovery of novel indole derivatives that inhibit NEDDylation and MAPK pathways against gastric cancer MGC803 cells

被引：27

作者：

Fu, Dong-Jun ^{[1
]}

Cui, Xin-Xin ^{[2
]}

Zhu, Ting ^{[2
]}

Zhang, Yan-Bing ^{[2
]}

Hu, Yang-Yang ^{[5
]}

Zhang, Li-Rong ^{[2
,3
,4
]}

Wang, Sheng-Hui ^{[2
,3
,4
]}

Zhang, Sai-Yang ^{[2
,3
,4
,6
]}

机构：

[1] Beijing Univ Chinese Med, Sch Chinese Mat Med, Modern Res Ctr Tradit Chinese Med, Beijing 100029, Peoples R China

[2] Zhengzhou Univ, Sch Basic Med Sci, Zhengzhou 450001, Peoples R China

[3] Zhengzhou Univ, Acad Med Sci, Zhengzhou 450001, Peoples R China

[4] Zhengzhou Univ, Henan Inst Adv Technol, Zhengzhou 450001, Peoples R China

[5] Univ Melbourne, Fac Sci, Melbourne, Vic 3010, Australia

[6] Nanjing Univ, State Key Lab Pharmaceut Biotechnol, Nanjing 210023, Jiangsu, Peoples R China

来源：

BIOORGANIC CHEMISTRY | 2021年 / 107卷

基金：

中国博士后科学基金;

关键词：

Indole; Apoptosis; NEDDylation pathway; MAPK pathway; MGC803; cells; ANTIPROLIFERATIVE ACTIVITY; DITHIOCARBAMATE HYBRIDS; DESIGN; APOPTOSIS; MIGRATION; KINASES; GROWTH; AGENTS;

D O I：

10.1016/j.bioorg.2021.104634

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：

A series of novel indole derivatives were synthesized and evaluated for their antiproliferative activity against three selected cancer cell lines (MGC803, EC-109 and PC-3). Among these analogues, 2-(5-methoxy-1H-indol-1-yl)-N-(4-methoxybenzyl)-N-(3,4,5-trimethoxyphenyeacetamide (V7) showed the best inhibitory activity against MGC803 cells with an IC50 value of 1.59 mu M. Cellular mechanisms elucidated that V7 inhibited colony formation, induced apoptosis and arrested cell cycle at G2/M phase. Importantly, indole analogue V7 inhibited NEDDy-lation pathway and MAPK pathway against MGC803 cells.

引用

页数：13

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