Molecular docking of the highly hypolipidemic agent alpha-asarone with the catalytic portion of HMG-CoA reductase.
Docking experiments using a number of published crystal structures of HMG-CoA reductase with the potent hypocholesterolemic agent alpha-asarone are described. The results indicate that alpha-asarone binds in the enzyme's active site. The methoxy groups play a key role in the binding and probably also in its biological activity, as shown by extensive SAR studies reported for analogues of alpha-asarone. The docking results will be valuable for the structure-based design of novel hypolipidemic agents.
Medina-Franco
José Luis
JL
Departamento de Farmacia, Facultad de Química, Universidad Nacional Autónoma de México, Circuito Exterior, Ciudad Universitaria, 04510 México, D.F., Mexico.
López-Vallejo
Fabián
F
Rodríguez-Morales
Sergio
S
Castillo
Rafael
R
Chamorro
Germán
G
Tamariz
Joaquín
J
D000081248:Allylbenzene Derivatives; D000840:Anisoles / Q000737:chemistry*; D001665:Binding Sites; D020134:Catalytic Domain; D003198:Computer Simulation; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D006903:Hydroxymethylglutaryl CoA Reductases / Q000737:chemistry*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000737:chemistry*; D008958:Models, Molecular; D011485:Protein Binding; D013329:Structure-Activity Relationship
D000081248:Allylbenzene Derivatives; D000840:Anisoles; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; C012195:asarone; D006903:Hydroxymethylglutaryl CoA Reductases