α-tocopheryl succinate as a scaffold to develop potent inhibitors of breast cancer cell adhesion

Dasheng Wang, Hsiao Ching Chuang, Shu Chuan Weng, Po Hsien Huang, Hao Yu Hsieh, Samuel K. Kulp, Ching Shih Chen

研究成果: Article

10 引文 斯高帕斯(Scopus)

摘要

This study is aimed at the pharmacological exploitation of α-tocopheryl succinate (1) to develop potent antiadhesion agents. Considering the structural cooperativity between the phytyl chain and the carboxylic terminus in determining the antiadhesion activity, our structural optimization led to compound 5 ([2-(4,8-dimethyl-non-1-enyl)-2,5,7,8- tetramethyl-chroman-6-yloxy]-acetic acid), which exhibited an-order-of-magnitude higher potency than 1 in blocking the adhesion of 4T1 metastatic breast cancer cells to extracellular matrix proteins (IC50, 0.6 μM versus 10 μM). Evidence indicates that the ability of compound 5 to block cell adhesion and migration was attributable to its effect on disrupting focal adhesion and actin cytoskeletal integrity by facilitating the degradation of focal adhesion kinase. Interactions between tumor cells and the ECM in the tumor microenvironment have been increasingly recognized as critical modulators of the metastatic potential of tumor cells. Consequently, the ability of compound 5 to block such interactions provides a unique pharmacological tool to shed light onto mechanisms that govern cell adhesion and tumor metastasis.

原文English
頁(從 - 到)5642-5648
頁數7
期刊Journal of Medicinal Chemistry
52
發行號18
DOIs
出版狀態Published - 2009 九月 24

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Drug Discovery

指紋 深入研究「α-tocopheryl succinate as a scaffold to develop potent inhibitors of breast cancer cell adhesion」主題。共同形成了獨特的指紋。

  • 引用此