Dihydroxylated 2,4,6-triphenyl pyridines: Synthesis, topoisomerase i and II inhibitory activity, cytotoxicity, and structure-activity relationship study

Radha Karki; Pritam Thapa; Han Young Yoo; Tara Man Kadayat; Pil Hoon Park; Youngwha Na; Eunyoung Lee; Kyung Hwa Jeon; Won Jea Cho; Heesung Choi; Youngjoo Kwon; Eung Seok Lee

doi:10.1016/j.ejmech.2012.01.015

Dihydroxylated 2,4,6-triphenyl pyridines: Synthesis, topoisomerase i and II inhibitory activity, cytotoxicity, and structure-activity relationship study

Radha Karki, Pritam Thapa, Han Young Yoo, Tara Man Kadayat, Pil Hoon Park, Youngwha Na, Eunyoung Lee, Kyung Hwa Jeon, Won Jea Cho, Heesung Choi, Youngjoo Kwon, Eung Seok Lee

Department of Pharmaceutical Sciences

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

78 Scopus citations

Abstract

Twelve dihydroxylated 2,4,6-triphenyl pyridines were designed and synthesized which contain hydroxyl groups at ortho, meta or para position of 2- and 6-phenyl, or 2- and 4-phenyl rings attached to the central pyridine. They were evaluated for topoisomerase I and II inhibitory activity, and cytotoxicity against several human cancer cell lines for the development of novel anticancer agents. Generally, dihydroxylated 2,4,6-triphenyl pyridines exhibited stronger topoisomerase II inhibitory activity, and cytotoxicity compared to those of monohydroxylated 2,4,6-triphenyl pyridines. The concrete structure-activity relationship was observed that dihydroxylated 2,4,6-triphenyl pyridines with hydroxyl group at meta or para position of 2-phenyl ring displayed significant topoisomerase II inhibitory activity as well as cytotoxicity. Positive correlation between topoisomerase II inhibitory activity and cytotoxicity was observed for compounds 10, 12, 13, 17-20 and 22.

Original language	English
Pages (from-to)	219-228
Number of pages	10
Journal	European Journal of Medicinal Chemistry
Volume	49
DOIs	https://doi.org/10.1016/j.ejmech.2012.01.015
State	Published - Mar 2012

Bibliographical note

Funding Information:
This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology ( 2009-0066925 , 2010-0002646 , and 2011-0001170 ).

Keywords

Anticancer agents
Cytotoxicity
Dihydroxylated 2,4,6-triphenyl pyridines
Topoisomerase I
Topoisomerase I.I.

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10.1016/j.ejmech.2012.01.015

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Karki, R., Thapa, P., Yoo, H. Y., Kadayat, T. M., Park, P. H., Na, Y., Lee, E., Jeon, K. H., Cho, W. J., Choi, H., Kwon, Y., & Lee, E. S. (2012). Dihydroxylated 2,4,6-triphenyl pyridines: Synthesis, topoisomerase i and II inhibitory activity, cytotoxicity, and structure-activity relationship study. European Journal of Medicinal Chemistry, 49, 219-228. https://doi.org/10.1016/j.ejmech.2012.01.015

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title = "Dihydroxylated 2,4,6-triphenyl pyridines: Synthesis, topoisomerase i and II inhibitory activity, cytotoxicity, and structure-activity relationship study",

abstract = "Twelve dihydroxylated 2,4,6-triphenyl pyridines were designed and synthesized which contain hydroxyl groups at ortho, meta or para position of 2- and 6-phenyl, or 2- and 4-phenyl rings attached to the central pyridine. They were evaluated for topoisomerase I and II inhibitory activity, and cytotoxicity against several human cancer cell lines for the development of novel anticancer agents. Generally, dihydroxylated 2,4,6-triphenyl pyridines exhibited stronger topoisomerase II inhibitory activity, and cytotoxicity compared to those of monohydroxylated 2,4,6-triphenyl pyridines. The concrete structure-activity relationship was observed that dihydroxylated 2,4,6-triphenyl pyridines with hydroxyl group at meta or para position of 2-phenyl ring displayed significant topoisomerase II inhibitory activity as well as cytotoxicity. Positive correlation between topoisomerase II inhibitory activity and cytotoxicity was observed for compounds 10, 12, 13, 17-20 and 22.",

keywords = "Anticancer agents, Cytotoxicity, Dihydroxylated 2,4,6-triphenyl pyridines, Topoisomerase I, Topoisomerase I.I.",

author = "Radha Karki and Pritam Thapa and Yoo, \{Han Young\} and Kadayat, \{Tara Man\} and Park, \{Pil Hoon\} and Youngwha Na and Eunyoung Lee and Jeon, \{Kyung Hwa\} and Cho, \{Won Jea\} and Heesung Choi and Youngjoo Kwon and Lee, \{Eung Seok\}",

note = "Funding Information: This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology ( 2009-0066925 , 2010-0002646 , and 2011-0001170 ).",

year = "2012",

month = mar,

doi = "10.1016/j.ejmech.2012.01.015",

language = "English",

volume = "49",

pages = "219--228",

journal = "European Journal of Medicinal Chemistry",

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Karki, R, Thapa, P, Yoo, HY, Kadayat, TM, Park, PH, Na, Y, Lee, E, Jeon, KH, Cho, WJ, Choi, H, Kwon, Y & Lee, ES 2012, 'Dihydroxylated 2,4,6-triphenyl pyridines: Synthesis, topoisomerase i and II inhibitory activity, cytotoxicity, and structure-activity relationship study', European Journal of Medicinal Chemistry, vol. 49, pp. 219-228. https://doi.org/10.1016/j.ejmech.2012.01.015

TY - JOUR

T1 - Dihydroxylated 2,4,6-triphenyl pyridines

T2 - Synthesis, topoisomerase i and II inhibitory activity, cytotoxicity, and structure-activity relationship study

AU - Karki, Radha

AU - Thapa, Pritam

AU - Yoo, Han Young

AU - Kadayat, Tara Man

AU - Park, Pil Hoon

AU - Na, Youngwha

AU - Lee, Eunyoung

AU - Jeon, Kyung Hwa

AU - Cho, Won Jea

AU - Choi, Heesung

AU - Kwon, Youngjoo

AU - Lee, Eung Seok

N1 - Funding Information: This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology ( 2009-0066925 , 2010-0002646 , and 2011-0001170 ).

PY - 2012/3

Y1 - 2012/3

N2 - Twelve dihydroxylated 2,4,6-triphenyl pyridines were designed and synthesized which contain hydroxyl groups at ortho, meta or para position of 2- and 6-phenyl, or 2- and 4-phenyl rings attached to the central pyridine. They were evaluated for topoisomerase I and II inhibitory activity, and cytotoxicity against several human cancer cell lines for the development of novel anticancer agents. Generally, dihydroxylated 2,4,6-triphenyl pyridines exhibited stronger topoisomerase II inhibitory activity, and cytotoxicity compared to those of monohydroxylated 2,4,6-triphenyl pyridines. The concrete structure-activity relationship was observed that dihydroxylated 2,4,6-triphenyl pyridines with hydroxyl group at meta or para position of 2-phenyl ring displayed significant topoisomerase II inhibitory activity as well as cytotoxicity. Positive correlation between topoisomerase II inhibitory activity and cytotoxicity was observed for compounds 10, 12, 13, 17-20 and 22.

AB - Twelve dihydroxylated 2,4,6-triphenyl pyridines were designed and synthesized which contain hydroxyl groups at ortho, meta or para position of 2- and 6-phenyl, or 2- and 4-phenyl rings attached to the central pyridine. They were evaluated for topoisomerase I and II inhibitory activity, and cytotoxicity against several human cancer cell lines for the development of novel anticancer agents. Generally, dihydroxylated 2,4,6-triphenyl pyridines exhibited stronger topoisomerase II inhibitory activity, and cytotoxicity compared to those of monohydroxylated 2,4,6-triphenyl pyridines. The concrete structure-activity relationship was observed that dihydroxylated 2,4,6-triphenyl pyridines with hydroxyl group at meta or para position of 2-phenyl ring displayed significant topoisomerase II inhibitory activity as well as cytotoxicity. Positive correlation between topoisomerase II inhibitory activity and cytotoxicity was observed for compounds 10, 12, 13, 17-20 and 22.

KW - Anticancer agents

KW - Cytotoxicity

KW - Dihydroxylated 2,4,6-triphenyl pyridines

KW - Topoisomerase I

KW - Topoisomerase I.I.

UR - https://www.scopus.com/pages/publications/84857239566

U2 - 10.1016/j.ejmech.2012.01.015

DO - 10.1016/j.ejmech.2012.01.015

M3 - Article

C2 - 22318164

AN - SCOPUS:84857239566

SN - 0223-5234

VL - 49

SP - 219

EP - 228

JO - European Journal of Medicinal Chemistry

JF - European Journal of Medicinal Chemistry

ER -

Dihydroxylated 2,4,6-triphenyl pyridines: Synthesis, topoisomerase i and II inhibitory activity, cytotoxicity, and structure-activity relationship study

Abstract

Bibliographical note

Keywords

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