Design, Synthesis and Anticancer Activity of Shikonin and Alkannin Derivatives with Different Substituents on the Naphthazarin Scaffold  

作　　者：ZHANG Xu CUI Jiahua ZHOU Wen LI Shaoshun 

机构地区：[1]School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, P.R.China

出　　处：《Chemical Research in Chinese Universities》2015年第3期394-400,共7页高等学校化学研究（英文版）

基　　金：the National Natural Science Foundation of China（No.81373274） and the State Key Laboratory Cultivatlon Base for the Chemistry and Molecular Engineering of Medicinal Resources, Ministry of Science and Technology of China （No.CHEMR2012-B08）.

摘　　要：Based on the asymmetric reduction of alkannin ketone derivative 4 by diisopinocampheylchloro- borane（DIP-C1）, a series of shikonin and alkannin derivatives was designed, synthesized and their anticancer activi- ties against various kinds of cell lines were evaluated. The in vitro biological experiments demonstrated that com- pound S-10, a 5,8-O-dimethyl-l,4-dioxime alkannin derivative, not only displayed excellent antiproliferative activity against cancer cells, but also exhibited 10w toxicity towards normal cells. It could induce HCT-116 cell apoptosis, but had no impact on the cell cycle. The underlying anticancer mechanism of S-10 is most likely different from other shikonin and alkannin derivatives.Based on the asymmetric reduction of alkannin ketone derivative 4 by diisopinocampheylchloro- borane（DIP-C1）, a series of shikonin and alkannin derivatives was designed, synthesized and their anticancer activi- ties against various kinds of cell lines were evaluated. The in vitro biological experiments demonstrated that com- pound S-10, a 5,8-O-dimethyl-l,4-dioxime alkannin derivative, not only displayed excellent antiproliferative activity against cancer cells, but also exhibited 10w toxicity towards normal cells. It could induce HCT-116 cell apoptosis, but had no impact on the cell cycle. The underlying anticancer mechanism of S-10 is most likely different from other shikonin and alkannin derivatives.

关 键 词：Shikonin and alkannin oxime derivative Asymmetric reduction ANTICANCER Apoptosis Cell cycle 

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