Design, synthesis and systematic evaluation of cytotoxic 3-heteroarylisoquinolinamines as topoisomerases inhibitors

Title
Design, synthesis and systematic evaluation of cytotoxic 3-heteroarylisoquinolinamines as topoisomerases inhibitors
Author(s)
이응석Hue Thi My Van[Hue Thi My Van]우현중[우현중]정형민[정형민]Daulat Bikram Khadka[Daulat Bikram Khadka]양수희[양수희]Chao Zhao[Chao Zhao]Yifeng Jin[Yifeng Jin]이광율[이광율]권영주[권영주]조원제[조원제]
Keywords
DNA TOPOISOMERASES; ANTICANCER AGENTS; ANTITUMOR AGENTS; I INHIBITORS; CANCER-CELLS; MECHANISM; CWJ-A-5; ROLES
Issue Date
201407
Publisher
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
Citation
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, v.82, pp.181 - 194
Abstract
A series of 3-heteroarylisoquinolinamines were designed, synthesized and evaluated for cytotoxicity, topoisomerases (topos) inhibitory activities and cell cycle inhibition. Several of the 3-heteroarylisoquinolines exhibited selective cytotoxicity against human ductal breast epithelial tumor (T47D) cells over non-cancerous human breast epithelial (MCF-10A) and human prostate cancer (DU145) cells. Most of the derivatives showed greater cytotoxicity in human colorectal adenocarcinoma (HCT-15) cells than camptothecin (CPT), etoposide and doxorubicin (DOX). Generally, 3-heteroarylisoquinolinamines displayed greater affinity for topo I than topo II. 3-Heteroarylisoquinolinamines with greater topo I inhibitory effect exhibited potent cytotoxicity. Piperazine-substituted derivative, 5b, with potent topo land moderate topo II activities intercalated between DNA bases and interacted with topos through H-bonds at the DNA cleavage site of a docking model. Moreover, flow cytometry indicated that cytotoxic 3-heteroarylisoquinolinamines led to accumulation of human cervical (HeLa) cancer cells in the different phases of the cell cycle before apoptosis. Taken together, 3-heteroarylisoquinolinamines possessed potent cytotoxicity with topos and cell cycle inhibitory activities. (C) 2014 Elsevier Masson SAS. All rights reserved.
URI
http://hdl.handle.net/YU.REPOSITORY/31508http://dx.doi.org/10.1016/j.ejmech.2014.05.047
ISSN
0223-5234
Appears in Collections:
약학대학 > 약학부 > Articles
Files in This Item:
There are no files associated with this item.
Export
RIS (EndNote)
XLS (Excel)
XML


qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

BROWSE