Institute of Chemistry, Academia Sinica, Taipei 115, Taiwan.
J Med Chem. 2011 Dec 22;54(24):8574-81. doi: 10.1021/jm201131n. Epub 2011 Nov 23.
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.
通过合理的设计方法，我们发现了一类新型 GST 抑制剂；我们报告了它们的发现、合成、抑制活性以及与顺铂联合对 A549 肺癌细胞系的协同作用。这一努力的结果表明，先导化合物 4-O-癸基-Gabosine D（24）在 A549 人肺腺上皮癌细胞中具有最佳的协同作用，并且这种活性涉及谷胱甘肽 S-转移酶 M1 的抑制，显然与 GSTM1 基因的 siRNA 介导的敲低一致。
