Synthesis and cytotoxic evaluation of N2-benzylated quaternary β-carboline amino acid ester conjugates

被引：19

作者：

Ma, Chunming ^{[1
]}

Cao, Rihui ^{[1
]}

Shi, Buxi ^{[1
]}

Li, Shaoxue ^{[1
]}

Chen, Zhiyong ^{[1
]}

Yi, Wei ^{[1
]}

Peng, Wenlie ^{[2
]}

Ren, Zhenhua ^{[2
]}

Song, Huacan ^{[1
]}

机构：

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

[2] Sun Yat Sen Univ, Sch Life Sci, Guangzhou 510275, Guangdong, Peoples R China

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2010年 / 45卷 / 04期

关键词：

Synthesis; beta-Carboline; Amino acid; Cytotoxic activity; SARs; CYCLIN-DEPENDENT KINASES; BENZODIAZEPINE RECEPTOR; HARMINE DERIVATIVES; ANTITUMOR AGENTS; ETHYL-ESTER; IN-VITRO; BINDING; DNA; ANALOGS; INHIBITORS;

D O I：

10.1016/j.ejmech.2009.12.060

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The beta-carboline alkaloids have been characterized as a class of potential antitumor agents. To further enhance the cytotoxic potency and improve water solubility of beta-carboline, a series of new beta-carboline amino acid ester, beta-carboline amino acid and N-2-benzylated quaternary beta-carboline amino acid ester conjugates were designed and synthesized, and the cytotoxic activities of these compounds were evaluated using a panel of human tumor cell lines. The N-2-benzylated quaternary beta-carboline amino acid ester conjugates represented the most interesting cytotoxic activities. Particularly, compounds 8b and 8g were found to be the most potent compounds with IC50 values lower than 20 mu M against all human tumor cell lines investigated. These results confirmed that the N-2-benzyl substituent on the beta-carboline ring played an important role in the modulation of the cytotoxic potencies. (C) 2010 Elsevier Masson SAS. All rights reserved.

引用

页码：1515 / 1523

页数：9

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