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

被引：75

作者：

Karki, Radha ^{[1
]}

Thapa, Pritam ^{[1
]}

Yoo, Han Young ^{[1
]}

Kadayat, Tara Man ^{[1
]}

Park, Pil-Hoon ^{[1
]}

Na, Youngwha ^{[2
]}

Lee, Eunyoung ^{[3
]}

Jeon, Kyung-Hwa ^{[3
]}

Cho, Won-Jea ^{[4
]}

Choi, Heesung ^{[5
]}

Kwon, Youngjoo ^{[3
]}

Lee, Eung-Seok ^{[1
]}

机构：

[1] Yeungnam Univ, Coll Pharm, Gyongsan 712749, South Korea

[2] Cha Univ, Coll Pharm, Pochon 487010, South Korea

[3] Ewha Womans Univ, Div Life & Pharmaceut Sci, Coll Pharm, Seoul 120750, South Korea

[4] Chonnam Natl Univ, Coll Pharm, Kwangju 500757, South Korea

[5] Eli Lilly Korea Ltd, Seoul 100958, South Korea

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2012年 / 49卷

基金：

新加坡国家研究基金会;

关键词：

Dihydroxylated 2,4,6-triphenyl pyridines; Topoisomerase I; Topoisomerase II; Cytotoxicity; Anticancer agents; DNA TOPOISOMERASES; DERIVATIVES; POISONS; ALPHA; CHALCONES; AGENTS;

D O I：

10.1016/j.ejmech.2012.01.015

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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. (C) 2012 Elsevier Masson SAS. All rights reserved.

引用

页码：219 / 228

页数：10

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