Design and synthesis of biotinylated dimethylation of alkannin oxime derivatives

详细信息    查看全文

• 作者：Guang Huang¹ ; Qing-Qing Meng¹ ; Wen Zhou ; Qi-Jing Zhang ; Jin-Yun Dong ; Shao-Shun Li ; ^{ssli@sjtu.edu.cn}
• 关键词：Alkannin and shikonin oxime derivatives ; Anticancer activity ; Biotin probe ; Molecular target ; Mitsunobu reaction
• 刊名：Chinese Chemical Letters
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：28
• 期：2
• 页码：453-457
• 全文大小：331 K
• 卷排序：28

文摘

DMAKO-05, a novel dimethylation of alkannin oxime derivative, exhibits remarkable anticancer activity as well as excellent cellular selectivity and thus has been considered as a promising antineoplastic agent for colorectal carcinoma and melanoma. However, its potent cytotoxicity is not closely associated with reactive oxygen species (ROS) and bioreductive alkylation. Its specific antitumor target(s) has still remained elusive. To recognize the molecular target(s) of DMAKO-05 and its analogs, four biotinylated DMAKO derivatives were designed and prepared. The biotin moiety was successfully introduced in the molecule through a modified Mitsunobu reaction, which kept its anticancer activity. Moreover, the cell-based investigation demonstrated that replacement of the linker C4 chain with another alkyl chain (C6 or C8) gave rise to the enhancement of cytotoxicity. Among these biotinyl derivatives, both compound 16 and 8c exhibited more potent anticancer activity than DMAKO-05 against MCF-7 cells and were comparatively effective to alkannin toward HCT-15 cells. As expected, they might be thought as ideal chemical probes. Collectively, our present work could provide an available approach for the identification of the potential antineoplastic target(s) of DMAKO derivatives.