Synthesis and biological evaluation of farnesylthiosalicylamides as potential anti-tumor agents

被引：15

作者：

Ling, Yong ^{[1
,2
]}

Wang, Zhiqiang ^{[1
,2
]}

Zhu, Hongyan ^{[2
]}

Wang, Xuemin ^{[2
]}

Zhang, Wei ^{[2
]}

Wang, Xinyang ^{[2
]}

Chen, Li ^{[1
]}

Huang, Zhangjian ^{[1
,3
]}

Zhang, Yihua ^{[1
,3
]}

机构：

[1] China Pharmaceut Univ, State Key Lab Nat Med, Nanjing 210009, Jiangsu, Peoples R China

[2] Nantong Univ, Coll Med, Nantong 226001, Peoples R China

[3] China Pharmaceut Univ, Ctr Drug Discovery, Nanjing 210009, Jiangsu, Peoples R China

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2014年 / 22卷 / 01期

关键词：

Farnesylthiosalicylic acid; Diamines; Cell apoptosis; Ras-related signaling pathway; Anti-cancer agents; ONCOGENIC RAS; TUMOR-GROWTH; SALIRASIB; DERIVATIVES;

D O I：

10.1016/j.bmc.2013.11.013

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Fourteen hybrids of farnesylthiosalicylic acid (FTS) with various diamines were synthesized and biologically evaluated. It was found that FTS-monoamide molecules (10a-g) displayed strong anti-proliferative activity against seven human cancer cell lines, superior to FTS and FTS-bisamide compounds (11a-g). The mono-amide 10f was the most active, with IC(50)s of 3.78-7.63 mu M against all tested cancer cells, even more potent than sorafenib (9.12-22.9 mu M). In addition, 10f induced SMMC-7721 cell apoptosis, down-regulated the expression of Bcl-2 and up-regulated Bax and caspase-3. Furthermore, 10f had the improved aqueous solubility relative to FTS. Finally, treatment with 10f dose-dependently inhibited the Ras-related signaling pathways in SMMC-7721 cells. Collectively, 10f could be a promising candidate for the intervention of human cancers. (C) 2013 Elsevier Ltd. All rights reserved.

引用

页码：374 / 380

页数：7

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