Synthesis and anti-glioblastoma effects of artemisinin-isothiocyanate derivatives.
Synthesis and anti-glioblastoma effects of artemisinin-isothiocyanate derivatives.
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青蒿素异硫氰酸酯衍生物的合成及其抗胶质母细胞瘤作用
DOI：
10.1039/c8ra08162j
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发表时间：
2018-12-04
期刊：
影响因子：
3.9
通讯作者：
He, Xixin
中科院分区：
文献类型：
--
作者：
Nyein, Chan Myae;Zhong, Xiaolin;Lu, Junfeng;Luo, Huijuan;Wang, Jiamin;Rapposelli, Simona;Li, Mingtao;Ying Ou-yang;Pi, Rongbiao;He, Xixin
合成了一系列含有异硫氰酸酯（ITC）基团的新型青蒿素（ART）衍生物。所有化合物在体外对多形性胶质母细胞瘤 U87 均表现出比母体双氢青蒿素 (DHA) 更有效的抗肿瘤作用。其中，5b的细胞毒活性最强，其作用呈浓度依赖性而非时间依赖性（24小时IC50为7.41μM，72小时IC50为7.35μM）。在 5b 处理的 U87 细胞中观察到固缩。 5b 诱导多种内在凋亡途径，包括 caspase 9 的上调、细胞色素 c 的释放、促凋亡蛋白 Bax 的增加、抗凋亡蛋白 Bcl 2 的减少以及通过 caspase 3 的上调激活执行途径。除了凋亡之外，自噬机制还通过上调LC3-II 的表达和 p62 的下调。此外，5b还显着减弱U87细胞的迁移。因此，我们的结果表明5b可能是进一步开发治疗胶质母细胞瘤新药的有前途的分子。青蒿素异硫氰酸酯衍生物的合成；评估这些化合物对 U87 人胶质母细胞瘤细胞的细胞毒性作用；化合物5b诱导U87细胞凋亡和自噬；化合物5b显着抑制U87细胞的迁移。
A series of novel artemisinin (ART) derivatives containing an isothiocyanate (ITC) group were synthesized. All the compounds showed more potent anti-tumor effects than those of parent dihydroartemisinin (DHA) towards glioblastoma multiforme U87 in vitro. Among them, 5b had the strongest cytotoxic activity which exerted its effects in a concentration-dependent but not time-dependent manner (IC50 7.41 μM for 24 h, 7.35 μM for 72 h). Pyknosis was observed in 5b-treated U87 cells. Multiple intrinsic apoptotic pathways were induced by 5b including the upregulation of caspase 9, the release of cytochrome c, an increase of the proapoptotic protein Bax, a decrease of the anti-apoptotic protein Bcl 2, and the activation of execution pathways by the upregulation of caspase 3. In addition to apoptosis, an autophagic mechanism was also involved in 5b-induced cytotoxicity to human GBM U87 cells by upregulating the expression of LC3-II and downregulating p62. Furthermore, 5b also significantly attenuated the migration of U87 cells. Therefore, our results suggest that 5b may be a promising molecule for the further development of a novel drug for the treatment of glioblastoma. Synthesis of artemisinin-isothiocyanate derivatives; evaluation of the cytotoxic effects of these compounds on U87 human glioblastoma cells; compound 5b induced apoptosis and autophagy in U87 cells; compound 5b significantly inhibited the migration of U87 cells.
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DOI：
10.3390/molecules22060773
发表时间：
2017-06-01
期刊：
Molecules (Basel, Switzerland)
影响因子：
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作者：
Luo B;Wang J;Li X;Lu W;Yang J;Hu Y;Huang P;Wen S
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158.5
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3.8
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DOI：
10.1158/1055-9965.epi-14-0275
发表时间：
2014-10
期刊：
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
影响因子：
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作者：
Thakkar JP;Dolecek TA;Horbinski C;Ostrom QT;Lightner DD;Barnholtz-Sloan JS;Villano JL
通讯作者：
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影响因子：
4.8
作者：
Morishima, N;Nakanishi, K;Yasuhiko, Y
通讯作者：
Yasuhiko, Y