Design, synthesis and biological evaluation of novel indole-based oxalamide and aminoacetamide derivatives as tubulin polymerization inhibitors

被引：22

作者：

Diao, Peng-Cheng ^{[1
]}

Jian, Xie-Er ^{[1
]}

Chen, Peng ^{[1
]}

Huang, Chuan ^{[1
]}

Yin, Jie ^{[1
]}

Huang, Jie Chun ^{[1
]}

Li, Jun-Sheng ^{[1
]}

Zhao, Pei-Liang ^{[1
]}

机构：

[1] Southern Med Univ, Sch Pharmaceut Sci, Guangdong Prov Key Lab New Drug Screening, Guangzhou 510515, Guangdong, Peoples R China

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2020年 / 30卷 / 02期

基金：

中国国家自然科学基金;

关键词：

Indoles; Synthesis; Tubulin polymerization; Antiproliferative activity; IN-VIVO; MICROTUBULE; RESISTANCE; EFFICACY; D-24851; UPDATE; AGENTS; CELLS;

D O I：

10.1016/j.bmcl.2019.126816

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of novel indole-based oxalamide and aminoacetamide derivatives were designed, synthesized, and evaluated for antiproliferative activities. Preliminary results revealed that compound 8g exhibited significant antiproliferative effect against PC-3, HeLa and HCT-116 cell lines. Flow cytometric analysis of the cell cycle demonstrated the compound 8g induced the cell cycle arrest at G2/M phase in HeLa cell lines. Immunocytochemistry revealed loss of intact microtubule structure in cells treated with 8g and inhibition of tubulin polymerization. Additionally, molecular docking analysis suggested that 8g formed stable interactions in the colchicine-binding site of tubulin. These preliminary results demonstrated that a new class of novel indole-based oxalamide and aminoacetamide derivatives described in the investigation could be developed as potential scaffolds to new anticancer agents.

引用

页数：6

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