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

Won-Jea Cho; Quynh Manh Le; Hue Thi My Van; Kwang Youl Lee; Bok Yun Kang; Eung-Seok Lee; Sang Kook Lee; Youngjoo Kwon

doi:10.1016/j.bmcl.2007.04.064

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

Bioorg Med Chem Lett. 2007 Jul 1;17(13):3531-4. doi: 10.1016/j.bmcl.2007.04.064. Epub 2007 Apr 25.

Authors

Won-Jea Cho¹, Quynh Manh Le, Hue Thi My Van, Kwang Youl Lee, Bok Yun Kang, Eung-Seok Lee, Sang Kook Lee, Youngjoo Kwon

Affiliation

¹ College of Pharmacy and Research Institute of Drug Development, Chonnam National University, Kwangju 500-757, Republic of Korea. wjcho@jnu.ac.kr <wjcho@jnu.ac.kr>

PMID: 17498951
DOI: 10.1016/j.bmcl.2007.04.064

Abstract

An intramolecular radical cyclization reaction of 4-bromo-3-arylisoquinolines 11a-c allowed the efficient synthesis of 11-methylindenoisoquinolines 2a-c. 5-(2-Aminoethylamino)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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Agents / pharmacology*
Cell Line, Tumor
Chemistry, Pharmaceutical / methods
DNA / chemistry
DNA Topoisomerases, Type I / chemistry
Drug Design
Drug Screening Assays, Antitumor*
Enzyme Inhibitors / pharmacology*
Humans
Inhibitory Concentration 50
Isoquinolines / chemistry*
Models, Chemical
Models, Molecular
Topoisomerase Inhibitors*
X-Rays

Substances

Antineoplastic Agents
Enzyme Inhibitors
Isoquinolines
Topoisomerase Inhibitors
DNA
DNA Topoisomerases, Type I