Novel synthetic 2-amino-10-(3,5-dimethoxy)benzyl-9(10H)-acridinone derivatives as potent DNA-binding antiproliferative agents

被引：49

作者：

Gao, Chunmei ^{[1
]}

Liu, Feng ^{[1
]}

Luan, Xudong ^{[1
]}

Tan, Chunyan ^{[1
]}

Liu, Hongxia ^{[1
]}

Xie, Yonghua ^{[1
]}

Jin, Yibao ^{[1
]}

Jiang, Yuyang ^{[1
,2
]}

机构：

[1] Tsinghua Univ, Grad Sch Shenzhen, Guangdong Prov Key Lab Chem Biol, Shenzhen 518055, Peoples R China

[2] Tsinghua Univ, Sch Med, Beijing 100084, Peoples R China

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2010年 / 18卷 / 21期

关键词：

Acridinone derivatives; Antiproliferative activity; DNA binding; Topoisomerase; 1; inhibitor; TOPOISOMERASE-I INHIBITORS; ACRIDONE DERIVATIVES; BIOLOGICAL EVALUATION; NS3; HELICASE; LUNG-CANCER; DESIGN; HOMOTRIPTYCENES; REPLICATION; ANALOGS; COMPLEX;

D O I：

10.1016/j.bmc.2010.08.058

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 9(10H)-acridinone derivatives with terminal amino substituents at C2 position on the acridinone ring were synthesized and studied for their antiproliferative activity and underlying mechanisms. These compounds demonstrated promising cytotoxicity to leukemia cells CCRF-CEM, displaying IC50 values in the low micromolar range. Structure-activity relationships (SAR) indicated that the compound 6d bearing a pyrrolidine substituent and 8a with a methyl ammonium side chain displayed higher cytotoxicity to CCRF-CEM cells and also solid tumor cells A549, HepG2, and MCF7. Furthermore, the compounds 6d and 8a had strong binding activity to calf thymus DNA (ct DNA), as detected by UV absorption and fluorescence quenching assays, but limited inhibitory activity to human topoisomerase 1 (topo 1). Taken together, this study discovered a series of new synthetic 9(10H)-acridinone derivatives with potent DNA binding and anticancer activity. (C) 2010 Elsevier Ltd. All rights reserved.

引用

页码：7507 / 7514

页数：8

共 35 条

[1] 1-[(omega-aminoalkyl)amino]-4-[N-(omega-aminaoalkyl)carbamoyl]-9-oxo-9,10-dihydroacridines as intercalating cytotoxic agents: Synthesis, DNA binding, and biological evaluation [J].