Departamento de Biología Molecular, Instituto Nacional de Cardiología Ignacio Chavéz, México D.F., Mexico.
Steroids. 2012 Apr;77(5):512-20. doi: 10.1016/j.steroids.2012.01.010. Epub 2012 Feb 2.
Compounds with estrogenic effects that also inhibit platelet aggregation might be useful in reducing thrombotic events associated with estrogenic therapy. In this study, two aminoestrogens, Buame [N-(3-hydroxy-1,3,5(10)-estratrien-17β-yl)-butylamine] and Diebud [N,N'-bis-(3-hydroxy-1,3,5(10)-estratrien-17β-yl)-1,4-butanediamine], were synthesized and characterized using common analytical methods and spectrophotometric analyses. The location and orientation of these molecules on the estrogenic receptor α (ERα) were also evaluated. Platelet inhibitory effects were elucidated ADP-induced platelet aggregation and ADP- and collagen-induced ATP release. Molecular docking demonstrated that Buame can reach and bind to the ERα in the ligand binding domain (LBD) similar to 17β-estradiol (co-crystallized ligand). On the other hand, Diebud binds only to the surface of ERα due to its high molecular volume compared to 17β-estradiol and Buame.
具有雌激素作用且能抑制血小板聚集的化合物可能有助于减少与雌激素治疗相关的血栓事件。在这项研究中，两种氨基雌激素 Buame[N-(3-羟基-1,3,5(10)-雌甾-17β-基)-丁基胺]和 Diebud[N,N'-双-(3-羟基-1,3,5(10)-雌甾-17β-基)-1,4-丁二胺]，通过常用的分析方法和分光光度分析进行了合成和表征。还评估了这些分子在雌激素受体α（ERα）上的位置和取向。通过 ADP 诱导的血小板聚集和 ADP 和胶原诱导的 ATP 释放，阐明了血小板抑制作用。分子对接表明，Buame 可以到达并结合到配体结合域（LBD）中的 ERα，类似于 17β-雌二醇（共结晶配体）。另一方面，由于分子体积大于 17β-雌二醇和 Buame，Diebud 仅结合到 ERα 的表面。
