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

Hue Thi My Van, Hyunjung Woo, Hyung Min Jeong, Daulat Bikram Khadka, Su Hui Yang, Chao Zhao, Yifeng Jin, Eung Seok Lee, Kwang Youl Lee, Youngjoo Kwon, Won Jea Cho

Research output: Contribution to journalArticlepeer-review

22 Scopus citations


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 I and 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.

Original languageEnglish
Pages (from-to)181-194
Number of pages14
JournalEuropean Journal of Medicinal Chemistry
StatePublished - 23 Jul 2014

Bibliographical note

Funding Information:
This work was supported by a grant from the Ministry of Health & Welfare, Republic of Korea . (Grant: HI12C1640 ).


  • 3-Heteroarylisoquinolinamine
  • Cell cycle arrest
  • Molecular docking
  • Selective cytotoxicity
  • Topoisomerase I
  • Topoisomerase II


Dive into the research topics of 'Design, synthesis and systematic evaluation of cytotoxic 3-heteroarylisoquinolinamines as topoisomerases inhibitors'. Together they form a unique fingerprint.

Cite this