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：

100705 [微生物与生化药学];

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

共 40 条

[1]

Dietary polyphenols as topoisomerase II poisons: B ring and C ring substituents determine the mechanism of enzyme-mediated DNA cleavage enhancement [J].

Bandele, Omari J. ;

Clawson, Sara J. ;

Osheroff, Neil .

CHEMICAL RESEARCH IN TOXICOLOGY, 2008, 21 (06) :1253-1260

[2]

(-)-epigallocatechin gallate, a major constituent of green tea, poisons human type II topoisomerases [J].

Bandele, Omari J. ;

Osheroff, Neil .

CHEMICAL RESEARCH IN TOXICOLOGY, 2008, 21 (04) :936-943

[3]

Bioflavonoids as poisons of human topoisomerase IIα and IIβ [J].

Bandele, Omari J. ;

Osheroff, Neil .

BIOCHEMISTRY, 2007, 46 (20) :6097-6108

[4]

2,4,6-Trisubstituted pyridines: Synthesis, topoisomerase I and II inhibitory activity, cytotoxicity, and structure-activity relationship [J].

Basnet, Arjun ;

Thapa, Pritam ;

Karki, Radha ;

Na, Younghwa ;

Jahng, Yurngdong ;

Jeong, Byeong-Seon ;

Jeong, Tae Cheon ;

Lee, Chong-Soon ;

Lee, Eung-Seok .

BIOORGANIC & MEDICINAL CHEMISTRY, 2007, 15 (13) :4351-4359

[5]

2,6-Dithienyl-4-furyl pyridines: Synthesis, topoisomerase I and II inhibition, cytotoxicity, structure-activity relationship, and docking study [J].

Basnet, Arjun ;

Thapa, Pritam ;

Karki, Radha ;

Choi, Hoyoung ;

Choi, Jae Hun ;

Yun, Minho ;

Jeong, Byeong-Seon ;

Jahng, Yurngdong ;

Na, Younghwa ;

Cho, Won-Jea ;

Kwon, Youngjoo ;

Lee, Chong-Soon ;

Lee, Eung-Seok .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2010, 20 (01) :42-47

[6]

Study on the substituents' effects of a series of synthetic chalcones against the yeast Candida albicans [J].

Batovska, D. ;

Parushev, St. ;

Slavova, A. ;

Bankova, V. ;

Tsvetkova, I. ;

Ninova, M. ;

Najdenski, H. .

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2007, 42 (01) :87-92

[7]

Curcumin, resveratrol and flavonoids as anti-inflammatory, cyto- and DNA-protective dietary compounds [J].

Bisht, Kavita ;

Wagner, Karl-Heinz ;

Bulmer, Andrew C. .

TOXICOLOGY, 2010, 278 (01) :88-100

[8]

Condensations. XI. Condensations of certain active hydrogen compounds effected by boron trifluoride and aluminum chloride [J].

Breslow, DS ;

Hauser, CR .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1940, 62 :2385-2388

[9]

Fukuda M, 1996, CANCER RES, V56, P789

[10]

Simple aromatic compounds containing propenone moiety show considerable dual COX/5-LOX inhibitory activities [J].

Jahng, Y ;

Zhao, LX ;

Moon, YS ;

Basnet, A ;

Kim, EK ;

Chang, HW ;

Ju, HK ;

Jeong, TC ;

Lee, ES .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2004, 14 (10) :2559-2562

← 1 2 3 4 →