title: Design, docking, and synthesis of novel indeno[1,2-c]isoquinolines for the development of antitumor agents as topoisomerase I inhibitors.
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.
authors.affiliation: 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>
authors.forename: Won-Jea
authors.initials: WJ
authors.lastname: Cho
authors.forename: Quynh Manh
authors.initials: QM
authors.lastname: Le
authors.forename: Hue Thi
authors.initials: HT
authors.lastname: My Van
authors.forename: Kwang
authors.initials: K
authors.lastname: Youl Lee
authors.forename: Bok Yun
authors.initials: BY
authors.lastname: Kang
authors.forename: Eung-Seok
authors.initials: ES
authors.lastname: Lee
authors.forename: Sang Kook
authors.initials: SK
authors.lastname: Lee
authors.forename: Youngjoo
authors.initials: Y
authors.lastname: Kwon
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical / Q000379:methods; D004247:DNA / Q000737:chemistry; D004264:DNA Topoisomerases, Type I / Q000737:chemistry; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D007546:Isoquinolines / Q000737:chemistry*; D008956:Models, Chemical; D008958:Models, Molecular; D059003:Topoisomerase Inhibitors; D014965:X-Rays
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D007546:Isoquinolines; D059003:Topoisomerase Inhibitors; D004247:DNA; D004264:DNA Topoisomerases, Type I