ABSTRACT
For the first time, structural information regarding the role of simvastatin in bone anabolism is described, and a bone-specific statin is introduced. Polyaspartate-conjugated simvastatin was synthesized by solid-phase synthesis with the assistance of microwave irradiation. It displays significant bone targeting and bone formation with less toxicity than simvastatin.
Subject(s)
Acyl Coenzyme A/metabolism , Anabolic Agents , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Simvastatin , Anabolic Agents/chemical synthesis , Anabolic Agents/chemistry , Anabolic Agents/pharmacology , Animals , Disease Models, Animal , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/chemical synthesis , Hydroxymethylglutaryl-CoA Reductase Inhibitors/chemistry , Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology , Liver/metabolism , Molecular Structure , Osteogenesis/drug effects , Simvastatin/analogs & derivatives , Simvastatin/chemical synthesis , Simvastatin/chemistry , Simvastatin/pharmacology , Solid-Phase Synthesis Techniques , ZebrafishABSTRACT
[Cu(Y)((G:2-6)-dendri-PAMAM-(Py)(n))](2Y+) complexes (3) were prepared, and their ability to generate oxygen radical anions was investigated. The maximum catalytic efficiency (k'(cat)/K(M)) was found to be 0.32 min(-1)·µM(-1), and a positive dendritic effect was observed. The saturated kinetics revealed that the improved catalytic efficiency resulted from an enhanced binding affinity toward molecular oxygen. FROM THE CLINICAL EDITOR: In this basic science study, the oxygen radical anion generating ability of specific copper complex of a pyridine-modified poly(amidoamine) dendrimer was investigated and reported in details.
