Design, synthesis and docking study of 5-amino substituted indeno[1,2-c]isoquinolines as novel topoisomerase I inhibitors

Daulat Bikram Khadka; Quynh Manh Le; Su Hui Yang; Hue Thi My Van; Thanh Nguyen Le; Suk Hee Cho; Youngjoo Kwon; Kyung-Tae Lee; Eung-Seok Lee; Won-Jea Cho

doi:10.1016/j.bmc.2011.01.064

Design, synthesis and docking study of 5-amino substituted indeno[1,2-c]isoquinolines as novel topoisomerase I inhibitors

Bioorg Med Chem. 2011 Mar 15;19(6):1924-9. doi: 10.1016/j.bmc.2011.01.064. Epub 2011 Feb 3.

Authors

Daulat Bikram Khadka¹, Quynh Manh Le, Su Hui Yang, Hue Thi My Van, Thanh Nguyen Le, Suk Hee Cho, Youngjoo Kwon, Kyung-Tae Lee, Eung-Seok 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: 21353568
DOI: 10.1016/j.bmc.2011.01.064

Abstract

Various 5-amino group-substituted indeno[1,2-c]isoquinolines 7a-f were synthesized based on the previous QSAR study as rigid structures of 3-arylisoquinolines. Amino group-substituted compounds, especially 5-piperazinyl indeno[1,2-c]isoquinoline 7f, displayed potent topoisomerase I inhibitory activity as well as cytotoxicities against five different tumor cell lines. A Surflex-Dock docking model of 7f was also studied.

Publication types

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

MeSH terms

Binding Sites
Cell Line, Tumor
Computer Simulation
DNA Topoisomerases, Type I / chemistry*
DNA Topoisomerases, Type I / metabolism
Drug Design
Humans
Isoquinolines / chemical synthesis
Isoquinolines / chemistry*
Isoquinolines / toxicity
Piperazines / chemical synthesis*
Piperazines / chemistry
Piperazines / toxicity
Quantitative Structure-Activity Relationship
Topoisomerase I Inhibitors / chemical synthesis*
Topoisomerase I Inhibitors / chemistry
Topoisomerase I Inhibitors / toxicity

Substances

5-piperazin-1-ylindeno(1,2-c)isoquinolin-11-one
Isoquinolines
Piperazines
Topoisomerase I Inhibitors
DNA Topoisomerases, Type I