具有雌激素和维生素 D2 的向量化二茂铁：合成、细胞毒性活性和对接研究。
Vectorized ferrocenes with estrogens and vitamin D2: synthesis, cytotoxic activity and docking studies.
机构信息
University of Puerto Rico, Department of Chemistry, PO Box 9019, Mayaguez, PR 00681.
出版信息
Dalton Trans. 2011 Oct 7;40(37):9557-65. doi: 10.1039/c1dt10995b. Epub 2011 Aug 18.
Abstract
Three ferrocene complexes vectorized with estrogens and vitamin D(2) were synthesized and fully characterized by spectroscopic, electrochemical and computational methods. The synthesis of these esters was accomplished by reacting ferrocenoyl chloride with the corresponding ROH groups (R = ergocalciferol, estradiol, estrone). The cytotoxicity of these complexes in HT-29 colon cancer and MCF-7 breast cancer cell lines was investigated in vitro. Only ferrocenoyl 17β-hydroxy-estra-1,3,5(10)-trien-3-olate showed good cytotoxic activity in both cell lines, exceeding those of ferrocenium and ferrocene. In MCF-7, ferrocenoyl 17β-hydroxy-estra-1,3,5(10)-trien-3-olate exhibited remarkable IC(50), in the low micromolar range. This may be attributed to the presence of the estradiol vector. Docking studies between alpha-estrogen receptor ligand binding site and ferrocenoyl 17β-hydroxy-estra-1,3,5(10)-trien-3-olate revealed some key hydrophobic interactions that might explain the cytotoxic activity of this ester.
摘要
三种雌激素和维生素 D（2）标记的二茂铁配合物已被合成，并通过光谱、电化学和计算方法进行了全面表征。这些酯的合成是通过使二茂铁酰氯与相应的 ROH 基团（R = 麦角钙化醇、雌二醇、雌酮）反应来完成的。这些配合物在 HT-29 结肠癌细胞系和 MCF-7 乳腺癌细胞系中的细胞毒性在体外进行了研究。只有二茂铁酰基 17β-羟基-雌-1,3,5(10)-三烯-3-醇酯在两种细胞系中均显示出良好的细胞毒性活性，超过了 ferrocenium 和 ferrocene。在 MCF-7 中，二茂铁酰基 17β-羟基-雌-1,3,5(10)-三烯-3-醇酯的 IC（50）值在低微摩尔范围内显著降低。这可能归因于雌二醇载体的存在。与α-雌激素受体配体结合位点之间的对接研究表明，ferrocenoyl 17β-羟基-雌-1,3,5(10)-三烯-3-醇酯存在一些关键的疏水相互作用，这可能解释了这种酯的细胞毒性活性。
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