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首页> 外文期刊>European Journal of Medicinal Chemistry: Chimie Therapeutique >Structural determinants of resveratrol for cell proliferation inhibition potency: experimental and docking studies of new analogs.
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Structural determinants of resveratrol for cell proliferation inhibition potency: experimental and docking studies of new analogs.

机译：白藜芦醇对细胞增殖抑制效能的结构决定因素：新类似物的实验和对接研究。

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摘要

Resveratrol is the subject of intense research because of the abundance of this compound in the human diet and as one of the most valuable natural chemopreventive agents. Further advances require new resveratrol analogs be used to identify the structural determinants of resveratrol for the inhibition potency of cell proliferation by comparing experimental and docking studies. Therefore, we synthesized new trans/(E)- and cis/(Z)-resveratrol - analogs not reported to date - by modifying the hydroxylation pattern of resveratrol and a double bond geometry. We included them in a larger panel of 14 molecules, including (Z)-3,5,4'-trimethoxystilbene, the most powerful molecule that is used as reference. Using a docking model complementary to experimental studies on the proliferation inhibition of the human colorectal tumor SW480 cell line, we show that methylation is the determinant substitution in inhibition efficacy, but only in molecules bearing a Z configuration. Most of the synthetic methylated derivatives (E or Z) stop mitosis at the M phase and lead to polyploid cells, while (E)-resveratrol inhibits cells at the S phase. Docking studies show that almost all of the docked structures of (Z)-polymethoxy isomers, but not most of the (E)-polymethoxy isomers substantially overlap the docked structure of combretastatin A-4, taken as reference ligand at the colchicine-tubulin binding site.
机译：白藜芦醇由于在人类饮食中含量丰富，是最有价值的天然化学预防剂之一，因此成为了研究的热点。进一步的进展要求通过比较实验和对接研究，将新的白藜芦醇类似物用于鉴定白藜芦醇的结构决定簇，以抑制细胞增殖。因此，我们通过修饰白藜芦醇的羟基化方式和双键几何结构，合成了新的反式/（E）-和顺式/（Z）-白藜芦醇-迄今为止尚未报道的类似物。我们将它们包含在一个由14个分子组成的更大的面板中，其中包括（Z）-3,5,4'-三甲氧基苯乙烯，这是用作参考的功能最强大的分子。使用对人类大肠肿瘤SW480细胞系的增殖抑制实验研究互补的对接模型，我们显示甲基化是抑制效力的决定性取代，但仅在具有Z构型的分子中。大多数合成的甲基化衍生物（E或Z）在M期阻止有丝分裂并导致多倍体细胞，而（E）-白藜芦醇在S期抑制细胞。对接研究表明，几乎所有（Z）-聚甲氧基异构体的对接结构，但不是大多数（E）-聚甲氧基异构体基本上与康美他汀A-4的对接结构重叠，在秋水仙碱-微管蛋白结合处作为参考配体现场。

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