Design, synthesis and biological evaluation of novel phthalazinone acridine derivatives as dual PARP and Topo inhibitors for potential anticancer agents

被引：22

作者：

Dai, Qiuzi ^{[1
,2
]}

Chen, Jiwei ^{[2
]}

Gao, Chunmei ^{[2
,3
]}

Sun, Qinsheng ^{[2
]}

Yuan, Zigao ^{[2
]}

Jiang, Yuyang ^{[2
,4
]}

机构：

[1] Tsinghua Univ, Dept Chem, Beijing 100084, Peoples R China

[2] Tsinghua Univ, Grad Sch Shenzhen, State Key Lab Chem Oncogen, Key Lab Chem Biol, Shenzhen 518055, Peoples R China

[3] Shenzhen Univ, Coll Chem & Chem Engn, Shenzhen 518060, Peoples R China

[4] Tsinghua Univ, Sch Med, Dept Pharmacol & Pharmaceut Sci, Beijing 100084, Peoples R China

来源：

CHINESE CHEMICAL LETTERS | 2020年 / 31卷 / 02期

关键词：

Topo; PARP; Multitarget; Acridines; Antitumor bioactivity; HYDROXAMIC ACID-DERIVATIVES; DNA-REPAIR; ANTIPROLIFERATIVE ACTIVITY; KINASE INHIBITORS; CANCER; BINDING; ROLES; DNMT;

D O I：

10.1016/j.cclet.2019.06.019

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

In this study, we designed and synthesized a series of phthalazinone acridine derivatives as dual PARP and Topo inhibitors. MTF assays indicated that most of the compounds significantly inhibited multiple cancer cells proliferation. In addition, all the compounds displayed Topo II inhibition activity at 10 mol/L, and also possessed good PARP-1 inhibitory activities. Subsequent mechanistic studies showed that compound 9a induced remarkable apoptosis and caused prominent S cell cycle arrest in HCT116 cells. Our study suggested that 9a inhibiting Topo and PARP concurrently can be a potential lead compound for cancer therapy. (C) 2019 Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences. Published by Elsevier B.V. All rights reserved.

引用

页码：404 / 408

页数：5

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