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Molecular design, synthesis and docking study of benz[b]oxepines and 12-oxobenzo[c]phenanthridinones as topoisomerase 1 inhibitors.

Abstract：

:Benz[b]oxepines 4a-g and 12-oxobenzo[c]phenanthridines 5a-d were designed and synthesized as constrained forms of 3-arylisoquinolines through an intramolecular radical cyclization reaction. Radical cyclization of O-vinyl compounds preferentially led to the 7-endo-trig cyclization pathway to the benz[b]oxepines and 12-oxobenzo[c]phenanthridines through 6-exo-trig path as minor products. Among the synthesized compounds, benz[b]oxepine derivative 4e exhibited potent in vitro cytotoxicity against three different tumor cell lines, as well as topoisomerase 1 inhibitory activity. A Surflex-Dock docking study was performed to clarify the topoisomerase 1 activity of 4e.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Lee SH,Van HT,Yang SH,Lee KT,Kwon Y,Cho WJ

doi

10.1016/j.bmcl.2009.03.058

subject

Has Abstract

pub_date

2009-05-01 00:00:00

pages

2444-7

issue

9

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(09)00368-0

journal_volume

19

pub_type

杂志文章

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