Novel myricetin derivatives: Design, synthesis and anticancer activity
Novel myricetin derivatives: Design, synthesis and anticancer activity
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新型杨梅素衍生物：设计、合成和抗癌活性
DOI：
10.1016/j.ejmech.2015.04.063
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发表时间：
2015-06-05
影响因子：
6.7
通讯作者：
Liu, Xin Hua
中科院分区：
文献类型：
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作者：
Xue, Wei;Song, Bao-An;Liu, Xin Hua
端粒和端粒酶与某些肿瘤的发生、发展密切相关。为了增强杨梅素部分抑制端粒酶的能力，我们在合理分析的基础上设计了一系列新型杨梅素衍生物。端粒酶抑制实验表明，化合物6d显示出最强的抑制活性，其IC_（50）值为0.91 μ M。抗癌活性测定表明，6d对人乳腺癌细胞MDA-MB-231表现出高活性。对化合物6d进行了分子对接模拟，得到了可能的结合模型，结果表明呋喃环深深插入到活性位点，与Phe 568、Pro 627残基发生疏水作用，四个甲氧基与Phe 568、Pro 627、Lys 902、瓦尔904和Pro 929残基发生疏水作用。Western blot结果显示化合物6d明显下调p65和TERT蛋白的表达。这些数据支持进一步研究更有效的p65和TERT调节剂的合理设计。(C)2015年Elsevier Masson SAS。All rights reserved.
Telomere and telomerase were closely related to occurrence and development of some cancers. To enhance ability of myricetin moiety for inhibiting telomerase, we designed a series of novel myricetin derivatives based on reasonable analysis. The telomerase inhibition assay showed that compound 6d displayed the most potent inhibitory activity with IC50 value of 0.91 mu M. The anticancer activity assay showed that 6d exhibited high activity against human breast cells MDA-MB-231. The docking simulation of compound 6d was performed to get the probable binding model, the results demonstrated that the furan ring inserted into the active site deeply and had hydrophobic interactions with residues of Phe 568, Pro 627, four methoxy groups had hydrophobic interactions with residues of Phe 568, Pro 627, Lys 902, Val 904 and Pro 929. Western blot results showed that expression of p65 and TERT protein was clearly down-regulated by compound 6d. These data support further studies for the rational design of more efficient p65 and TERT modulators. (C) 2015 Elsevier Masson SAS. All rights reserved.