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

Suh Hee Lee; Hue Thi My Van; Su Hui Yang; Kyung Tae Lee; Youngjoo Kwon; Won Jea Cho

doi:10.1016/j.bmcl.2009.03.058

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

Suh Hee Lee, Hue Thi My Van, Su Hui Yang, Kyung Tae Lee, Youngjoo Kwon, Won Jea Cho

Department of Pharmaceutical Sciences

Research output: Contribution to journal › Article › peer-review

46 Scopus citations

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.

Original language	English
Pages (from-to)	2444-2447
Number of pages	4
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	19
Issue number	9
DOIs	https://doi.org/10.1016/j.bmcl.2009.03.058
State	Published - 1 May 2009

Bibliographical note

Funding Information:
This work was supported by a Korea Research Foundation Grant (KRF-2007-521-E00190).

Keywords

Cytotoxicity
Docking study
Inhibitor
Molecular modeling
Radical cyclization
Synthesis
Topoisomerase 1

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title = "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.",

keywords = "Cytotoxicity, Docking study, Inhibitor, Molecular modeling, Radical cyclization, Synthesis, Topoisomerase 1",

author = "Lee, {Suh Hee} and Van, {Hue Thi My} and Yang, {Su Hui} and Lee, {Kyung Tae} and Youngjoo Kwon and Cho, {Won Jea}",

note = "Funding Information: This work was supported by a Korea Research Foundation Grant (KRF-2007-521-E00190).",

year = "2009",

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doi = "10.1016/j.bmcl.2009.03.058",

language = "English",

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journal = "Bioorganic and Medicinal Chemistry Letters",

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AU - Lee, Suh Hee

AU - Van, Hue Thi My

AU - Yang, Su Hui

AU - Lee, Kyung Tae

AU - Kwon, Youngjoo

AU - Cho, Won Jea

N1 - Funding Information: This work was supported by a Korea Research Foundation Grant (KRF-2007-521-E00190).

PY - 2009/5/1

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N2 - 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.

AB - 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.

KW - Cytotoxicity

KW - Docking study

KW - Inhibitor

KW - Molecular modeling

KW - Radical cyclization

KW - Synthesis

KW - Topoisomerase 1

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JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 9

ER -

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

Abstract

Bibliographical note

Keywords

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