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.
Won-Jea Cho  1 ,  Quynh Manh Le ,  Hue Thi My Van ,  Kwang Youl Lee ,  Bok Yun Kang ,  Eung-Seok Lee ,  Sang Kook Lee ,  Youngjoo Kwon
Affiliations
  • 1. College of Pharmacy and Research Institute of Drug Development, Chonnam National University, Kwangju 500-757, Republic of Korea. [email protected]
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.