Hydroxylated 2,4-diphenyl indenopyridine derivatives as a selective non-intercalative topoisomerase catalytic inhibitor

Tara Man Kadayat; Chanmi Park; Kyu Yeon Jun; Til Bahadur Thapa Magar; Ganesh Bist; Han Young Yoo; Youngjoo Kwon; Eung Seok Lee

doi:10.1016/j.ejmech.2014.11.046

Hydroxylated 2,4-diphenyl indenopyridine derivatives as a selective non-intercalative topoisomerase catalytic inhibitor

Tara Man Kadayat, Chanmi Park, Kyu Yeon Jun, Til Bahadur Thapa Magar, Ganesh Bist, Han Young Yoo, Youngjoo Kwon, Eung Seok Lee

Department of Pharmaceutical Sciences

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

34 Scopus citations

Abstract

For the development of novel anticancer agents, we designed and synthesized hydroxylated 2,4-diphenyl indenopyridines, and evaluated their topoisomerase inhibitory activity as well as their antiproliferative activities against several human cancer cell lines. The structure-activity relationship study showed that indenopyridines with hydroxyl group at meta or para positions of 2-or 4-phenyl ring displayed selective and significant topoisomerase IIα (topo IIα) inhibitory activity and potent antiproliferative activity. Positive correlation between topo IIα inhibition and antiproliferative activity was observed for compounds 15, 16, 18-20, 22, 23, 25 and 26. The mode of action of compound 16 was further evaluated to be a non-intercalativetopo IIα catalytic inhibitor.

Original language	English
Pages (from-to)	302-314
Number of pages	13
Journal	European Journal of Medicinal Chemistry
Volume	90
DOIs	https://doi.org/10.1016/j.ejmech.2014.11.046
State	Published - Jan 2015

Bibliographical note

Funding Information:
This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology ( NRF-2012R1A2A2A01046188 ).

Publisher Copyright:
© 2014 Elsevier Masson SAS.

Keywords

Anticancer agents
Hydroxylated 2,4-diphenyl indenopyridine
Terpyridine
Topoisomerase IIa non-intercalative
catalytic inhibitorAntiproliferative activity

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title = "Hydroxylated 2,4-diphenyl indenopyridine derivatives as a selective non-intercalative topoisomerase catalytic inhibitor",

abstract = "For the development of novel anticancer agents, we designed and synthesized hydroxylated 2,4-diphenyl indenopyridines, and evaluated their topoisomerase inhibitory activity as well as their antiproliferative activities against several human cancer cell lines. The structure-activity relationship study showed that indenopyridines with hydroxyl group at meta or para positions of 2-or 4-phenyl ring displayed selective and significant topoisomerase IIα (topo IIα) inhibitory activity and potent antiproliferative activity. Positive correlation between topo IIα inhibition and antiproliferative activity was observed for compounds 15, 16, 18-20, 22, 23, 25 and 26. The mode of action of compound 16 was further evaluated to be a non-intercalativetopo IIα catalytic inhibitor.",

keywords = "Anticancer agents, Hydroxylated 2,4-diphenyl indenopyridine, Terpyridine, Topoisomerase IIa non-intercalative, catalytic inhibitorAntiproliferative activity",

author = "Kadayat, {Tara Man} and Chanmi Park and Jun, {Kyu Yeon} and {Thapa Magar}, {Til Bahadur} and Ganesh Bist and Yoo, {Han Young} and Youngjoo Kwon and Lee, {Eung Seok}",

note = "Funding Information: This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology ( NRF-2012R1A2A2A01046188 ). Publisher Copyright: {\textcopyright} 2014 Elsevier Masson SAS.",

year = "2015",

month = jan,

doi = "10.1016/j.ejmech.2014.11.046",

language = "English",

volume = "90",

pages = "302--314",

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T1 - Hydroxylated 2,4-diphenyl indenopyridine derivatives as a selective non-intercalative topoisomerase catalytic inhibitor

AU - Kadayat, Tara Man

AU - Park, Chanmi

AU - Jun, Kyu Yeon

AU - Thapa Magar, Til Bahadur

AU - Bist, Ganesh

AU - Yoo, Han Young

AU - Kwon, Youngjoo

AU - Lee, Eung Seok

N1 - Funding Information: This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology ( NRF-2012R1A2A2A01046188 ). Publisher Copyright: © 2014 Elsevier Masson SAS.

PY - 2015/1

Y1 - 2015/1

N2 - For the development of novel anticancer agents, we designed and synthesized hydroxylated 2,4-diphenyl indenopyridines, and evaluated their topoisomerase inhibitory activity as well as their antiproliferative activities against several human cancer cell lines. The structure-activity relationship study showed that indenopyridines with hydroxyl group at meta or para positions of 2-or 4-phenyl ring displayed selective and significant topoisomerase IIα (topo IIα) inhibitory activity and potent antiproliferative activity. Positive correlation between topo IIα inhibition and antiproliferative activity was observed for compounds 15, 16, 18-20, 22, 23, 25 and 26. The mode of action of compound 16 was further evaluated to be a non-intercalativetopo IIα catalytic inhibitor.

AB - For the development of novel anticancer agents, we designed and synthesized hydroxylated 2,4-diphenyl indenopyridines, and evaluated their topoisomerase inhibitory activity as well as their antiproliferative activities against several human cancer cell lines. The structure-activity relationship study showed that indenopyridines with hydroxyl group at meta or para positions of 2-or 4-phenyl ring displayed selective and significant topoisomerase IIα (topo IIα) inhibitory activity and potent antiproliferative activity. Positive correlation between topo IIα inhibition and antiproliferative activity was observed for compounds 15, 16, 18-20, 22, 23, 25 and 26. The mode of action of compound 16 was further evaluated to be a non-intercalativetopo IIα catalytic inhibitor.

KW - Anticancer agents

KW - Hydroxylated 2,4-diphenyl indenopyridine

KW - Terpyridine

KW - Topoisomerase IIa non-intercalative

KW - catalytic inhibitorAntiproliferative activity

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JF - European Journal of Medicinal Chemistry

ER -

Hydroxylated 2,4-diphenyl indenopyridine derivatives as a selective non-intercalative topoisomerase catalytic inhibitor

Abstract

Bibliographical note

Keywords

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