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新型二氢吡唑基和吡唑基青蒿素-苯醚的设计、合成及其在癌细胞中的抗增殖活性

[Design, synthesis and antiproliferative activity in cancer cells of novel dihydropyrazolyl and pyrazolyl artemisinin-phenyl ethers].

作者信息

Wei Yun-Fei, Huang Min, Li Ai-Hua, Zhao Feng, Zhong Hang, Liu Dan, Zhao Lin-Xiang

机构信息

Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, China.

出版信息

Zhongguo Zhong Yao Za Zhi. 2018 Sep;43(17):3582-3588. doi: 10.19540/j.cnki.cjcmm.20180613.002.

Abstract

To explore potent anticancer agent based on artemisinin scaffold, a series of 10--phenyl ethers derivatives containing dihydropyrazolyl or pyrazolyl moiety have been designed and synthesized. Their structures were determined by LC-MS and ¹H-NMR date. Inhibitory effects of the target compounds in human breast cancer MCF-7, MCF/Adr, MDA-MB-231 cells and prostate cell line PC-3 were determined by MTT assay. Those derivatives displayed good antiproliferative activity against the tested cancer cells. Particularly, target compounds exhibited significant cytotoxicity against drug-resistance cells MCF/Adr, which was worthy for further investigation.

摘要

为了探索基于青蒿素骨架的高效抗癌剂,设计并合成了一系列含有二氢吡唑基或吡唑基部分的10-苯基醚衍生物。通过液相色谱-质谱联用(LC-MS)和¹H-核磁共振(¹H-NMR)数据确定了它们的结构。采用MTT法测定了目标化合物对人乳腺癌MCF-7、MCF/Adr、MDA-MB-231细胞和前列腺癌细胞系PC-3的抑制作用。这些衍生物对受试癌细胞显示出良好的抗增殖活性。特别是,目标化合物对耐药细胞MCF/Adr表现出显著的细胞毒性,值得进一步研究。

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