Design, docking, and synthesis of novel indeno[1,2-c]isoquinolines for the development of antitumor agents as topoisomerase I inhibitors

被引：52
作者：
Cho, Won-Jea [1 ]
Le, Quynh Manh
Van, Hue Thi My
Lee, Kwang Youl
Kang, Bok Yun
Lee, Eung-Seok
Lee, Sang Kook
Kwon, Youngjoo
机构：
[1] Chonnam Natl Univ, Coll Pharm, Kwangju 500757, South Korea
[2] Chonnam Natl Univ, Res Inst Drug Dev, Kwangju 500757, South Korea
[3] Yeungnam Univ, Coll Pharm, Kyongsan 712749, South Korea
[4] Ewha Womans Univ, Coll Pharm, Seoul 120750, South Korea
来源：
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2007年 / 17卷 / 13期
基金：
新加坡国家研究基金会;
关键词：
COVALENT; DNA;
D O I：
10.1016/j.bmcl.2007.04.064
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
An intramolecular radical cyclization reaction of 4-bromo-3-arylisoquinolines 11a-c allowed the efficient synthesis of 11-methylindenoisoquinolines 2a-c. 5-(2-Aminoethylainino)indeno[1,2-c]isoquinolin-11-one 4 was also prepared in the convenient manner. The synthesized compounds were tested in vitro for cytotoxicity and DNA-topoisomerase 1 (top 1) inhibitory activity. The dramatic enhancement of top 1 inhibitory activity of 4 was explained by a docking study using the FlexX program. (c) 2007 Elsevier Ltd. All rights reserved.
引用
收藏
页码：3531 / 3534
页数：4
相关论文
共 14 条
[1]   Synthesis of new 3-arylisoquinolinamines: Effect on topoisomerase I inhibition and cytotoxicity [J].
Cho, WJ ;
Min, SY ;
Le, TN ;
Kim, TS .
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2003, 13 (24) :4451-4454
[2]   Molecular Modeling of 3-arylisoquinoline antitumor agents active against A-549. A comparative molecular field analysis study [J].
Cho, WJ ;
Kim, EK ;
Park, IY ;
Jeong, EY ;
Kim, TS ;
Le, TN ;
Kim, DD ;
Leed, ES .
BIOORGANIC & MEDICINAL CHEMISTRY, 2002, 10 (09) :2953-2961
[3]   Synthesis and biological evaluation of 3-arylisoquinolines as antitumor agents [J].
Cho, WJ ;
Park, MJ ;
Chung, BH ;
Lee, CO .
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1998, 8 (01) :41-46
[4]  
Cho WJ, 2000, B KOR CHEM SOC, V21, P1035
[5]  
Hardman WE, 1999, ANTICANCER RES, V19, P2269
[6]   Human topoisomerase I inhibition: Docking camptothecin and derivatives into a structure-based active site model [J].
Laco, GS ;
Collins, JR ;
Luke, BT ;
Kroth, H ;
Sayer, JM ;
Jerina, DM ;
Pommier, Y .
BIOCHEMISTRY, 2002, 41 (05) :1428-1435
[7]   A versatile total synthesis of benzo[c]phenanthridine and protoberberine alkaloids using lithiated toluamide-benzonitrile cycloaddition [J].
Le, TN ;
Gang, SG ;
Cho, WJ .
JOURNAL OF ORGANIC CHEMISTRY, 2004, 69 (08) :2768-2772
[8]   A systematic study of nitrated indenoisoquinolines reveals a potent topoisomerase I inhibitor [J].
Morrell, Andrew ;
Antony, Smitha ;
Kohlhagen, Glenda ;
Pommier, Yves ;
Cushman, Mark .
JOURNAL OF MEDICINAL CHEMISTRY, 2006, 49 (26) :7740-7753
[9]   Synthesis and evaluation of indenoisoquinoline topoisomerase I inhibitors substituted with nitrogen heterocycles [J].
Nagarajan, Muthukaman ;
Morrell, Andrew ;
Ioanoviciu, Alexandra ;
Antony, Smitha ;
Kohlhagen, Glenda ;
Agama, Keli ;
Hollingshead, Melinda ;
Pommier, Yves ;
Cushman, Mark .
JOURNAL OF MEDICINAL CHEMISTRY, 2006, 49 (21) :6283-6289
[10]   Mechanisms of resistance to topoisomerase I-targeting drugs [J].
Rasheed, ZA ;
Rubin, EH .
ONCOGENE, 2003, 22 (47) :7296-7304
12