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-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.

► We presented the molecular structure of two aminoestrogens, Buame and Diebud. ► Platelet inhibitory effects were elucidated by aggregation and ATP release. ► The location and orientation of these molecules on the ERα also were evaluated.