The structures and inhibitory effects of 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] on platelet aggregation.

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-17 beta-yl)-butylamine] and Diebud [N,N'-bis-(3-hydroxy-1,3,5(10)-estratrien-17 beta-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 alpha (ER alpha) 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 ER alpha in the ligand binding domain (LBD) similar to 17 beta-estradiol (co-crystallized ligand). On the other hand, Diebud binds only to the surface of ER alpha due to its high molecular volume compared to 17 beta-estradiol and Buame. (C) 2012 Elsevier Inc. All rights reserved.