Novel Nitric Oxide-Releasing Derivatives of Farnesylthiosalicylic Acid: Synthesis and Evaluation of Antihepatocellular Carcinoma Activity

被引：61

作者：

Ling, Yong ^{[1
,2
]}

Ye, Xiaolei ^{[3
]}

Zhang, Zhenzhen ^{[1
]}

Zhang, Yihua ^{[1
]}

Lai, Yisheng ^{[1
]}

Ji, Hui ^{[1
]}

Peng, Sixun ^{[1
]}

Tian, Jide ^{[4
]}

机构：

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

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

[3] Ningbo Univ, Ningbo Inst Med Sci, Ningbo 315000, Zhejiang, Peoples R China

[4] Univ Calif Los Angeles, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2011年 / 54卷 / 09期

关键词：

HUMAN HEPATOCELLULAR-CARCINOMA; RAS GENE; IN-VIVO; HA-RAS; K-RAS; GROWTH; ACTIVATION; PATHWAYS; CANCER; CELLS;

D O I：

10.1021/jm1014814

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Novel furoxan-based nitric oxide (NO) releasing derivatives (8a-p) of farnesylthiosalicylic acid (FTS) were synthesized. Compound 8l displayed the strongest inhibition on the proliferation of human hepatocellular carcinoma (HCC) cells in vitro, superior to FTS, sorafenib, and furoxan moiety, selectively induced high frequency of HCC cell apoptosis, and produced high levels of NO in HCC cells but not in nontumor liver cells. Furthermore, 8l exhibited low acute toxicity to mice and significantly inhibited the growth of HCC tumors in vivo and the Ras-related signaling in the tumors. Therefore, our novel findings may provide a new framework for the design of new NO-releasing furoxan/FTS hybrids for the intervention of human HCC.

引用

页码：3251 / 3259

页数：9

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