Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Ampl. Polifunzionale, Via P. Bucci, 87036 Rende (CS), Italy.
CNR-NANOTEC, Licryl-UOS Cosenza and CEMIF.Cal, Department of Physics, University of Calabria, Via P. Bucci, 87036 Rende (CS), Italy.
Molecules. 2018 Apr 12;23(4):894. doi: 10.3390/molecules23040894.
The physiological responses to estrogen hormones are mediated within specific tissues by at least two distinct receptors, ER and ER. Several natural and synthetic molecules show activity by interacting with these proteins. In particular, a number of vegetal compounds known as phytoestrogens shows estrogenic or anti-estrogenic activity. The majority of these compounds belongs to the isoflavones family and the most representative one, genistein, shows anti-proliferative effects on various hormone-sensitive cancer cells, including breast, ovarian and prostate cancer. In this work we describe the identification of structurally related homoisoflavones isolated from (L.) Parl. (), a perennial bulbous plant, potentially useful as hormonal substitutes or complements in cancer treatments. Two of these compounds have been selected as potential ligands of estrogen receptors (ERs) and the interaction with both isoforms of estrogen receptors have been investigated through molecular docking on their crystallographic structures. The results provide evidence of the binding of these compounds to the target receptors and their interactions with key residues of the active sites of the two proteins, and thus they could represent suitable leads for the development of novel tools for the dissection of ER signaling and the development of new pharmacological treatments in hormone-sensitive cancers.
雌激素激素的生理反应是由至少两种不同的受体（ER 和 ER）在特定组织中介导的。一些天然和合成分子通过与这些蛋白质相互作用显示出活性。特别是，一些被称为植物雌激素的植物化合物具有雌激素或抗雌激素活性。这些化合物中的大多数属于异黄酮家族，其中最具代表性的染料木黄酮对各种激素敏感的癌细胞（包括乳腺癌、卵巢癌和前列腺癌）具有抗增殖作用。在这项工作中，我们描述了从（L.）Parl.（）中分离出的结构相关的同型异黄酮的鉴定，（）是一种多年生鳞茎植物，可能可作为癌症治疗中激素替代物或补充物。选择其中两种化合物作为雌激素受体（ERs）的潜在配体，并通过对其晶体结构进行分子对接研究了它们与两种雌激素受体亚型的相互作用。结果提供了这些化合物与靶受体结合的证据，以及它们与两种蛋白质活性部位关键残基的相互作用，因此它们可能代表开发用于解析 ER 信号和开发激素敏感癌症新的药理学治疗方法的新型工具的合适先导物。
