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

doi:10.1007/s40242-015-4385-y

Chemical Research in Chinese Universities ›› 2015, Vol. 31 ›› Issue (3): 394-400.doi: 10.1007/s40242-015-4385-y

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

ZHANG Xu, CUI Jiahua, ZHOU Wen, LI Shaoshun

School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, P. R. China

Received:2014-10-14 Revised:2014-12-12 Online:2015-06-01 Published:2014-12-22
Contact: LI Shaoshun E-mail:ssli@sjtu.edu.cn
Supported by:
Supported by the National Natural Science Foundation of China(No.81373274) and the State Key Laboratory Cultivation Base for the Chemistry and Molecular Engineering of Medicinal Resources, Ministry of Science and Technology of China (No.CHEMR2012-B08).

Abstract

Abstract:

Based on the asymmetric reduction of alkannin ketone derivative 4 by diisopinocampheylchloro-borane(DIP-Cl), a series of shikonin and alkannin derivatives was designed, synthesized and their anticancer activities against various kinds of cell lines were evaluated. The in vitro biological experiments demonstrated that compound S-10, a 5,8-O-dimethyl-1,4-dioxime alkannin derivative, not only displayed excellent antiproliferative activity against cancer cells, but also exhibited low 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.

Key words: Shikonin and alkannin oxime derivative, Asymmetric reduction, Anticancer, Apoptosis, Cell cycle

ZHANG Xu, CUI Jiahua, ZHOU Wen, LI Shaoshun. Design, Synthesis and Anticancer Activity of Shikonin and Alkannin Derivatives with Different Substituents on the Naphthazarin Scaffold[J]. Chemical Research in Chinese Universities, 2015, 31(3): 394-400.

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

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