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新型冬凌草甲素衍生物通过自噬依赖性细胞死亡抑制癌症。

Novel dauricine derivatives suppress cancer via autophagy-dependent cell death.

机构信息

State Key Laboratory of Quality Research in Chinese Medicine, and Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Taipa, Macau.

State Key Laboratory of Quality Research in Chinese Medicine, and Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Taipa, Macau.

出版信息

Bioorg Chem. 2019 Mar;83:450-460. doi: 10.1016/j.bioorg.2018.10.074. Epub 2018 Nov 2.

Abstract

Eleven dauricine derivatives were synthesized and evaluated for their anti-cancer effect in different cancer cells and their autophagic activity in HeLa model cell. Among these newly synthesized compounds, carbamates 2a, 2b, carbonyl ester 3a and sulfonyl ester 4a exhibited potent cytotoxic effects on tested cancer cells with IC values ranged from 2.72 to 12.53 μM, which were more potent than that of dauricine (higher than 15.53 μM). The above four derivatives are validated to induce autophagy-dependent cell death in HeLa cancer cells. These findings offer us a promising source for generating novel autophagic enhancers for anti-cancer therapy.

摘要

合成了 11 种冬凌草衍生化合物,并评估了它们在不同癌细胞中的抗癌效果及其在 HeLa 模型细胞中的自噬活性。在所合成的化合物中,氨基甲酸酯 2a、2b、羰基酯 3a 和砜基酯 4a 对测试的癌细胞表现出强烈的细胞毒性作用,IC 值范围为 2.72 至 12.53μM,比冬凌草(高于 15.53μM)更有效。验证了上述四个衍生物可诱导 HeLa 癌细胞发生自噬依赖性细胞死亡。这些发现为开发新型自噬增强剂用于癌症治疗提供了有前途的来源。

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