268202-08-0Relevant articles and documents
Design, synthesis, and docking of highly hypolipidemic agents: Schizosaccharomyces pombe as a new model for evaluating α-asarone-based HMG-CoA reductase inhibitors
Argueelles, Nancy,Sanchez-Sandoval, Eugenia,Mendieta, Aaron,Villa-Tanaca, Lourdes,Garduno-Siciliano, Leticia,Jimenez, Fabiola,Cruz, Maria del Carmen,Medina-Franco, Jose L.,Chamorro-Cevallos, German,Tamariz, Joaquin
scheme or table, p. 4238 - 4248 (2010/09/12)
A series of α-asarone-based analogues was designed by conducting docking experiments with published crystal structures of human HMG-CoA reductase. Indeed, synthesis and evaluation of this series showed a highly hypocholesterolemic in vivo activity in a murine model, as predicted by previous docking studies. In agreement with this model, the polar groups attached to the benzene ring could play a key role in the enzyme binding and probably also in its biological activity, mimicking the HMG-moiety of the natural substrate. The hypolipidemic action mechanism of these compounds was investigated by developing a simple, efficient, and novel model for determining HMG-CoA reductase inhibition. The partial purification of the enzyme from Schizosaccharomyces pombe allowed for testing of α-asarone- and fibrate-based analogues, resulting in positive and significant inhibitory activity.
