Structural modification of 3-arylisoquinolines to isoindolo[2,1-b]isoquinolinones for the development of novel topoisomerase 1 inhibitors with molecular docking study

Hue Thi My Van; Won-Jea Cho

doi:10.1016/j.bmcl.2009.03.042

Structural modification of 3-arylisoquinolines to isoindolo[2,1-b]isoquinolinones for the development of novel topoisomerase 1 inhibitors with molecular docking study

Bioorg Med Chem Lett. 2009 May 1;19(9):2551-4. doi: 10.1016/j.bmcl.2009.03.042. Epub 2009 Mar 16.

Authors

Hue Thi My Van¹, Won-Jea Cho

Affiliation

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

PMID: 19328687
DOI: 10.1016/j.bmcl.2009.03.042

Abstract

Isoindolo[2,1-b]isoquinolinones 9a-i were designed and synthesized as constrained forms of 3-arylisoquinolines through an intramolecular cyclization reaction. Among the synthesized compounds, 9d exhibited potent topoisomerase 1 inhibitory activity with cytotoxicities against three different tumor cell lines. A Surflex-dock docking study was performed to clarify the topoisomerase 1 inhibitory activity of 9d.

Publication types

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

MeSH terms

Antineoplastic Agents / chemical synthesis*
Antineoplastic Agents / pharmacology
Camptothecin / chemistry
Camptothecin / pharmacology
Cell Line, Tumor
Chemistry, Pharmaceutical / methods*
Drug Design
Drug Screening Assays, Antitumor
Humans
Isoquinolines / chemistry*
Models, Chemical
Molecular Conformation
Molecular Structure
Topoisomerase I Inhibitors*

Substances

Antineoplastic Agents
Isoquinolines
Topoisomerase I Inhibitors
Camptothecin