Design, docking, and synthesis of novel indeno[1,2-c]isoquinolines for the development of antitumor agents as topoisomerase I inhibitors

Won Jea Cho; Quynh Manh Le; Hue Thi My Van; Kwang Youl Lee; Bok Yun Kang; Eung Seok Lee; Sang Kook Lee; Youngjoo Kwon

doi:10.1016/j.bmcl.2007.04.064

Design, docking, and synthesis of novel indeno[1,2-c]isoquinolines for the development of antitumor agents as topoisomerase I inhibitors

Won Jea Cho, Quynh Manh Le, Hue Thi My Van, Kwang Youl Lee, Bok Yun Kang, Eung Seok Lee, Sang Kook Lee, Youngjoo Kwon

Department of Pharmaceutical Sciences

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

51 Scopus citations

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.

Original language	English
Pages (from-to)	3531-3534
Number of pages	4
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	17
Issue number	13
DOIs	https://doi.org/10.1016/j.bmcl.2007.04.064
State	Published - 1 Jul 2007

Bibliographical note

Funding Information:
Financial support from the Korea Research Foundation (KRF-2003-041-E00336) of Korea is greatly appreciated.

Keywords

Antitumor agents
Docking study
FlexX
Indeno[1,2-c]isoquinolines
Synthesis of isoquinolines
Topoisomerase 1 inhibitor

Access to Document

10.1016/j.bmcl.2007.04.064

Cite this

@article{cd76f8fe07504c4699d9e01e27918e5b,

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.",

keywords = "Antitumor agents, Docking study, FlexX, Indeno[1,2-c]isoquinolines, Synthesis of isoquinolines, Topoisomerase 1 inhibitor",

author = "Cho, {Won Jea} and Le, {Quynh Manh} and {My Van}, {Hue Thi} and {Youl Lee}, Kwang and Kang, {Bok Yun} and Lee, {Eung Seok} and Lee, {Sang Kook} and Youngjoo Kwon",

note = "Funding Information: Financial support from the Korea Research Foundation (KRF-2003-041-E00336) of Korea is greatly appreciated.",

year = "2007",

month = jul,

day = "1",

doi = "10.1016/j.bmcl.2007.04.064",

language = "English",

volume = "17",

pages = "3531--3534",

journal = "Bioorganic and Medicinal Chemistry Letters",

issn = "0960-894X",

publisher = "Elsevier Ltd.",

number = "13",

}

TY - JOUR

T1 - Design, docking, and synthesis of novel indeno[1,2-c]isoquinolines for the development of antitumor agents as topoisomerase I inhibitors

AU - Cho, Won Jea

AU - Le, Quynh Manh

AU - My Van, Hue Thi

AU - Youl Lee, Kwang

AU - Kang, Bok Yun

AU - Lee, Eung Seok

AU - Lee, Sang Kook

AU - Kwon, Youngjoo

N1 - Funding Information: Financial support from the Korea Research Foundation (KRF-2003-041-E00336) of Korea is greatly appreciated.

PY - 2007/7/1

Y1 - 2007/7/1

N2 - 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.

AB - 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.

KW - Antitumor agents

KW - Docking study

KW - FlexX

KW - Indeno[1,2-c]isoquinolines

KW - Synthesis of isoquinolines

KW - Topoisomerase 1 inhibitor

UR - http://www.scopus.com/inward/record.url?scp=34250168713&partnerID=8YFLogxK

U2 - 10.1016/j.bmcl.2007.04.064

DO - 10.1016/j.bmcl.2007.04.064

M3 - Article

C2 - 17498951

AN - SCOPUS:34250168713

SN - 0960-894X

VL - 17

SP - 3531

EP - 3534

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 13

ER -

Design, docking, and synthesis of novel indeno[1,2-c]isoquinolines for the development of antitumor agents as topoisomerase I inhibitors

Abstract

Bibliographical note

Keywords

Access to Document

Fingerprint

Cite this