Synthesis and Evaluation of Anticancer Activity of New 4-Acyloxy Derivatives of Robustic Acid
Synthesis and Evaluation of Anticancer Activity of New 4-Acyloxy Derivatives of Robustic Acid
复制标题
新型强效酸4-酰氧基衍生物的合成及抗癌活性评价。
DOI：
10.3390/ijms20215336
复制
发表时间：
2019-11-01
影响因子：
5.6
通讯作者：
Liang, Yan
中科院分区：
文献类型：
--
作者：
Chen, Rui;Huo, Lini;Liang, Yan
本研究合成了一系列4-酰氧基玫瑰酸衍生物，并对其进行了表征，以评价其抗癌活性。其结构经质谱学(MS)、核磁共振波谱(核磁共振)确证。得到了其中一种化合物的单晶X射线衍射结构，为进一步验证目标化合物的结构奠定了基础。分别对人白血病细胞HL-60、人非小细胞肺癌细胞A-549、人肝癌细胞SMMC-7721、人肝癌细胞HepG2和人宫颈癌细胞Hela进行了抗肿瘤活性评价。其中三个化合物在体外表现出很强的细胞毒性和优异的DNA拓扑异构酶I抑制活性，即使在0.1 mM的浓度下也是如此。最值得注意的是其中两种化合物对正常细胞的轻微毒性，其活性与癌细胞中的阳性对照相似。通过Surflex-Dock对接实验研究了所有化合物的拓扑异构酶I活性。在所有其他化合物中，选择最敏感的化合物进一步研究其对HL-60细胞的诱导凋亡和细胞周期调节的作用。我们的结果表明，这些化合物的抗癌作用可以归因于它们对拓扑异构酶I、细胞凋亡和细胞周期的药理作用。这些发现表明，玫瑰花酸衍生物可能被用作潜在的抗肿瘤药物。
In the present study, a series of 4-acyloxy robustic acid derivatives were synthesized and characterized for evaluation of their anti-cancer activity. The structures of these derivatives were elucidated by mass spectra (MS) nuclear magnetic resonance spectra (NMR). The single-crystal X-ray diffraction structure of one of these compounds was obtained, for further validation of the target compound structures. The anticancer activities of the target products were evaluated against human leukemic cells HL-60, human non-small cell lung carcinoma cells A-549, human hepatic carcinoma cells SMMC-7721, human hepatocellular carcinoma cells HepG2, and human cervical carcinoma cells Hela. Three compounds among them exhibited potent in-vitro cytotoxicity and excellent DNA topoisomerase I inhibitory activity, even at 0.1 mM concentrations. The most noteworthy observation was the minor toxicity of two of these compounds to normal cells, with an activity similar to the positive control in cancerous cells. A Surflex-Dock docking study was performed to investigate the topoisomerase I activity of all compounds. Of all the other compounds, the most sensitive compound was selected for further investigation of its effect on apoptosis induction and cell cycle regulation in HL-60 cells. Our results suggest that the anticancer effects of these compounds can be attributed to their pharmacological effects on topoisomerase I, cell apoptosis, and cell cycle. These findings suggest that robustic acid derivatives could be used as potential antitumor drugs.