Synthesis and in Vitro Biological Evaluation of Hybrids from Tetrahydro-β-carboline and Hydroxylcinnamic Acid as Antitumor Carcinoma Agents

被引：16

作者：

Lin, Ying ^{[1
]}

Xia, Xuanping ^{[2
]}

Yao, Rongxin ^{[1
]}

Ni, Li ^{[3
]}

Hu, Jie ^{[4
]}

Guo, Wenjian ^{[1
]}

Zhu, Baoling ^{[1
]}

机构：

[1] Wenzhou Med Univ, Affiliated Hosp 2, Dept Hematol & Oncol, Wenzhou 325035, Zhejiang, Peoples R China

[2] Wenzhou Med Univ, Affiliated Hosp 2, Dept Gastroenterol, Wenzhou 325035, Zhejiang, Peoples R China

[3] Wenzhou Med Univ, Affiliated Hosp 2, Dept Clin Lab, Wenzhou 325035, Zhejiang, Peoples R China

[4] Wenzhou Med Univ, Dept Pharm, Wenzhou 325035, Zhejiang, Peoples R China

来源：

CHEMICAL & PHARMACEUTICAL BULLETIN | 2014年 / 62卷 / 04期

关键词：

synthesis; tetrahydro-beta-carboline; hydroxylcinnamic acid; anti-tumor agent; inhibitory activity; cell apoptosis; FERULIC ACID; DESIGN; ANALOGS; DERIVATIVES; ALKALOIDS; CELLS;

D O I：

10.1248/cpb.c13-00902

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Novel hybrids 8a-j and 9a-j were designed and synthesized by coupling the carboxyl group of hydroxylcinnamic acids with tetrahydro-beta-carboline alkaloids which were linked with different substituted nitrogen-containing heterocycles at the positions-N9, and their in vitro biological activities were evaluated. It was found that most hybrids showed good to moderate anti-tumor activities. Especially, compound 9j had a great potency superior to 5-fluorouracil (5-FU) and comparable to adriamycin in human cancer cells, and could selectively inhibit tumor cells, but not inhibit non-tumor cell proliferation in vitro. More importantly, apoptosis assay indicated that 9j could significantly induce tumor cell apoptosis in a dose-dependent manner. Therefore, our novel findings may provide a new framework for the design of new hybrids for the intervention of human cancers.

引用

页码：343 / 349

页数：7

共 24 条

[1] Bioengineering Strategies for Designing Targeted Cancer Therapies [J].

Alexander-Bryant, Angela A. ;

Vanden Berg-Foels, Wendy S. ;

Wen, Xuejun .

ADVANCES IN CANCER RESEARCH, VOL 118, 2013, 118 :1-59

[2] Ferulic Acid Inhibits 7,12-Dimethylbenz[a] anthracene-Induced Hamster Buccal Pouch Carcinogenesis [J].

Balakrishnan, Subramanian ;

Menon, Venugopal P. ;

Manoharan, Shanmugam .

JOURNAL OF MEDICINAL FOOD, 2008, 11 (04) :693-700

[3]

Bharate SB, 2012, MINI-REV MED CHEM, V12, P650

[4] Design, synthesis and cardioprotective effect of a new class of dual-acting agents:: Phenolic tetrahydro-β-carboline RGD peptidomimetic conjugates [J].

Bi, Wei ;

Cai, Jianhui ;

Liu, Sanguang ;

Baudy-Floc'h, Michele ;

Bi, Lanrong .

BIOORGANIC & MEDICINAL CHEMISTRY, 2007, 15 (22) :6909-6919

[5]

Bombrun A., 2001, U.S. Patent, Patent No. [6, 306, 870B1, 6306870]

[6] Azatoxin is a mechanistic hybrid of the topoisomerase II-targeted anticancer drugs etoposide and ellipticine [J].

Cline, SD ;

Macdonald, TL ;

Osheroff, N .

BIOCHEMISTRY, 1997, 36 (42) :13095-13101

[7] Hybrid Compound Design To Overcome the Gatekeeper T338M Mutation in cSrc [J].

Getlik, Matthaeus ;

Gruetter, Christian ;

Simard, Jeffrey R. ;

Klueter, Sabine ;

Rabiller, Matthias ;

Rode, Haridas B. ;

Robubi, Armin ;

Rauh, Daniel .

JOURNAL OF MEDICINAL CHEMISTRY, 2009, 52 (13) :3915-3926

[8] Design of β-carboline derivatives as DNA-targeting antitumor agents [J].

Guan, Huaji ;

Chen, Hongsheng ;

Peng, Wenlie ;

Ma, Yan ;

Cao, Rihui ;

Liu, Xiaodong ;

Xu, Anlong .

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2006, 41 (10) :1167-1179

[9] Oxidative Metabolism of the Bioactive and Naturally Occurring β-Carboline Alkaloids, Norharman and Harman, by Human Cytochrome P450 Enzymes [J].

Herraiz, Tomas ;

Guillen, Hugo ;

Aran, Vicente J. .

CHEMICAL RESEARCH IN TOXICOLOGY, 2008, 21 (11) :2172-2180

[10] Natural Phenolic Compounds From Medicinal Herbs and Dietary Plants: Potential Use for Cancer Prevention [J].

Huang, Wu-Yang ;

Cai, Yi-Zhong ;

Zhang, Yanbo .

NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL, 2010, 62 (01) :1-20

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