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.
Departamento de Biología Molecular, Instituto Nacional de Cardiología Ignacio Chavéz, México D.F., Mexico.
Mirthala
M
Flores-García
Juan M
JM
Fernández-G
Mireille
M
León-Martínez
Simón
S
Hernández-Ortega
Oscar
O
Pérez-Méndez
José
J
Correa-Basurto
Elizabeth
E
Carreón-Torres
Luis E
LE
Tolentino-López
Guillermo Manuel
GM
Ceballos-Reyes
Aurora
A
de la Peña-Díaz
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000378:metabolism; D000328:Adult; D001665:Binding Sites; D003094:Collagen / Q000494:pharmacology; D018360:Crystallography, X-Ray; D004305:Dose-Response Relationship, Drug; D045166:Estradiol Congeners / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D047628:Estrogen Receptor alpha / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008081:Liposomes / Q000737:chemistry; D008297:Male; D008875:Middle Aged; D008958:Models, Molecular; D015394:Molecular Structure; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D055815:Young Adult
D045166:Estradiol Congeners; D047628:Estrogen Receptor alpha; D008081:Liposomes; C574241:N,N'-bis-(3-hydroxy-1,3,5(10)-estratrien-17beta-yl)-1,4-butanediamine; D010975:Platelet Aggregation Inhibitors; C083897:buame; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D003094:Collagen