Citation: Huang Guang, Meng Qing-Qing, Zhou Wen, Zhang Qi-Jing, Dong Jin-Yun, Li Shao-Shun. Design and synthesis of biotinylated dimethylation of alkannin oxime derivatives[J]. Chinese Chemical Letters, ;2017, 28(2): 453-457. doi: 10.1016/j.cclet.2016.09.015 shu

Design and synthesis of biotinylated dimethylation of alkannin oxime derivatives

School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China

Corresponding author: Li Shao-Shun, ssli@sjtu.edu.cn

Received Date: 25 July 2016
Revised Date: 29 August 2016
Accepted Date: 6 September 2016
Available Online: 1 March 2016

Figures(3)

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 cellbased 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.
- Alkannin and shikonin oxime derivatives,
- Anticancer activity,
- Biotin probe,
- Molecular target,
- Mitsunobu reaction
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