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

@article{ddd0d6b4c5cf4e9da85e517c4f46779e,

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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