Convenient synthesis of indeno[1,2-c]isoquinolines as constrained forms of 3-arylisoquinolines and docking study of a topoisomerase I inhibitor into DNA-topoisomerase I complex

Hue Thi My Van; Quynh Manh Le; Kwang Youl Lee; Eung-Seok Lee; Youngjoo Kwon; Tae Sung Kim; Thanh Nguyen Le; Suh-Hee Lee; Won-Jea Cho

doi:10.1016/j.bmcl.2007.08.062

Convenient synthesis of indeno[1,2-c]isoquinolines as constrained forms of 3-arylisoquinolines and docking study of a topoisomerase I inhibitor into DNA-topoisomerase I complex

Bioorg Med Chem Lett. 2007 Nov 1;17(21):5763-7. doi: 10.1016/j.bmcl.2007.08.062. Epub 2007 Aug 29.

Authors

Hue Thi My Van¹, Quynh Manh Le, Kwang Youl Lee, Eung-Seok Lee, Youngjoo Kwon, Tae Sung Kim, Thanh Nguyen Le, Suh-Hee Lee, Won-Jea Cho

Affiliation

¹ College of Pharmacy and Research Institute of Drug Development, Chonnam National University, Gwangju 500-757, Republic of Korea.

PMID: 17827007
DOI: 10.1016/j.bmcl.2007.08.062

Abstract

11-hydroxyindeno[1,2-c]isoquinolines 12a-c were prepared as constrained forms of 3-arylisoquinolines through an intramolecular cyclization reaction. Among the synthesized compounds, the 11-(i)butoxy analog 15l displayed potent in vitro cytotoxicity against four different tumor cell lines as well as topoisomerase 1 inhibitory activity. A FlexX docking study was performed to explain the topoisomerase 1 activity of 15l.

Publication types

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

MeSH terms

Cell Line, Tumor
DNA Topoisomerases, Type I / chemistry
Enzyme Inhibitors / chemical synthesis*
Enzyme Inhibitors / chemistry
Enzyme Inhibitors / pharmacology
Humans
Hydrogen Bonding
Isoquinolines / chemical synthesis*
Isoquinolines / chemistry
Isoquinolines / pharmacology
Models, Molecular
Molecular Structure
Topoisomerase I Inhibitors*

Substances

Enzyme Inhibitors
Isoquinolines
Topoisomerase I Inhibitors
DNA Topoisomerases, Type I