Synthesis, cytotoxic activities and DNA binding properties of β-carboline derivatives

被引：47

作者：

Chen, Zhiyong ^{[1
]}

Cao, Rihui ^{[1
]}

Yu, Liang ^{[1
]}

Shi, Buxi ^{[1
]}

Sun, Jie ^{[2
]}

Guo, Liang ^{[2
]}

Ma, Qin ^{[2
]}

Yi, Wei ^{[1
]}

Song, Xiao ^{[1
]}

Song, Huacan ^{[1
]}

机构：

[1] Sun Yat Sen Univ, Sch Chem & Chem Engn, Guangzhou 510275, Guangdong, Peoples R China

[2] Xinjiang Huashidan Pharmaceut Co Ltd, Urumqi 830011, Peoples R China

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2010年 / 45卷 / 11期

关键词：

beta-Carboline; Synthesis; Cytotoxic; Intercalating; T-m; CYCLIN-DEPENDENT KINASES; ACID ETHYL-ESTER; ANTITUMOR AGENTS; HARMINE DERIVATIVES; IN-VITRO; RECEPTORS; INHIBITORS; ANALOGS; NORHARMAN; DESIGN;

D O I：

10.1016/j.ejmech.2010.07.037

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

In a continuing effort to develop novel beta-carbolines endowed with better pharmacological profile, a series of water-soluble beta-carbolines bearing a flexible amino side chain was designed and synthesized, and the cytotoxic activities in vitro of these compounds were evaluated. The N-9-arylated alkyl substituted beta-carbolines represented the most interesting cytotoxic agents, and compounds 4c and 4d were found to be the most potent compounds with IC50 values lower than 10 mu M against ten human tumor cell lines. The results confirmed that the N-9-arylated alkyl substituents of beta-carboline played a very important role in the modulation of the cytotoxic potencies. In addition, the interaction with DNA of these compounds was also investigated, these compounds were found to exhibit significant DNA binding affinity. (C) 2010 Elsevier Masson SAS. All rights reserved.

引用

页码：4740 / 4745

页数：6

共 34 条

[1] HYPOTHERMIC EFFECT OF HARMALA ALKALOID IN RATS - INVOLVEMENT OF SEROTONERGIC MECHANISM [J].

ABDELFATTAH, AFM ;

MATSUMOTO, K ;

GAMMAZ, HAK ;

WATANABE, H .

PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR, 1995, 52 (02) :421-426

[2] PREDICTIVE BINDING OF BETA-CARBOLINE INVERSE AGONISTS AND ANTAGONISTS VIA THE COMFA GOLPE APPROACH [J].

ALLEN, MS ;

LALOGGIA, AJ ;

DORN, LJ ;

MARTIN, MJ ;

COSTANTINO, G ;

HAGEN, TJ ;

KOEHLER, KF ;

SKOLNICK, P ;

COOK, JM .

JOURNAL OF MEDICINAL CHEMISTRY, 1992, 35 (22) :4001-4010

[3] The discovery of tetrahydro-β-carbolines as inhibitors of the kinesin Eg5 [J].

Barsanti, Paul A. ;

Wang, Weibo ;

Ni, Zhi-Jie ;

Duhl, David ;

Brammeier, Nathan ;

Martin, Eric ;

Bussiere, Dirksen ;

Walter, Annette O. .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2010, 20 (01) :157-160

[4] Synthesis and biological studies of 1-amino β-carbolines [J].

Boursereau, Y ;

Coldham, I .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2004, 14 (23) :5841-5844

[5] Design, synthesis and in vitro and in vivo antitumor activities of novel β-carboline derivatives [J].

Cao, R ;

Chen, H ;

Peng, W ;

Ma, Y ;

Hou, X ;

Guan, H ;

Liu, X ;

Xu, A .

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2005, 40 (10) :991-1001

[6] DNA binding properties of 9-substituted harmine derivatives [J].

Cao, RH ;

Peng, WL ;

Chen, HS ;

Ma, Y ;

Liu, XD ;

Hou, XR ;

Guan, HJ ;

Xu, AL .

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2005, 338 (03) :1557-1563

[7] Synthesis and in vitro cytotoxic evaluation of 1,3-bisubstituted and 1,3,9-trisubstituted β-carboline derivatives [J].

Cao, RH ;

Peng, WL ;

Chen, HS ;

Hou, XR ;

Guan, HJ ;

Chen, Q ;

Ma, Y ;

Xu, AL .

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2005, 40 (03) :249-257

[8] Synthesis, acute toxicities, and antitumor effects of novel 9-substituted β-carboline derivatives [J].

Cao, RH ;

Chen, Q ;

Hou, XR ;

Chen, HS ;

Guan, HJ ;

Ma, Y ;

Peng, WL ;

Xu, AL .

BIOORGANIC & MEDICINAL CHEMISTRY, 2004, 12 (17) :4613-4623

[9] Synthesis and cytotoxic activities of 1-benzylidine substituted β-carboline derivatives [J].

Cao, Rihui ;

Yi, Wei ;

Wu, Qifeng ;

Guan, Xiangdong ;

Feng, Manxiu ;

Ma, Chunming ;

Chen, Zhiyong ;

Song, Huacan ;

Peng, Wenlie .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2008, 18 (24) :6558-6561

[10] β-Carboline alkaloids:: Biochemical and pharmacological functions [J].

Cao, Rihui ;

Peng, Wenlie ;

Wang, Zihou ;

Xu, Anlong .

CURRENT MEDICINAL CHEMISTRY, 2007, 14 (04) :479-500

← 1 2 3 4 →