Inhibition of Glutathione S-Transferase M1 by New Gabosine Analogues Is Essential for Overcoming Cisplatin Resistance in Lung Cancer Cells

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• 作者：Chie-Hong Wang ; Ho T. Wu ; Hau M. Cheng ; Tien-Jui Yen ; I-Hsuan Lu ; Hui Chuan Chang ; Shu-Chuan Jao ; Tony K. M. Shing ; Wen-Shan Li
• 刊名：Journal of Medicinal Chemistry
• 出版年：2011
• 出版时间：December 22, 2011
• 年：2011
• 卷：54
• 期：24
• 页码：8574-8581
• 全文大小：423K
• 年卷期：v.54,no.24(December 22, 2011)
• ISSN：1520-4804

文摘

A new class of human GST inhibitors has been identified via rational design approach; we report their discovery, synthesis, inhibitory activity, and synergetic effect in combination with cisplatin against A549 lung cancer cell line. The results of this effort show that the lead 4-O-decyl-gabosine D (24) has optimum synergetic effect in A549 human lung adenocarcinoma epithelial cell and that this activity involves inhibition of glutathione S-transferase M1, apparently consistent with siRNA-mediated knockdown of GSTM1 gene.